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Moreno F, Méndez L, Fernández I, Miralles-Pérez B, Giralt M, Romeu M, Ramos-Romero S, Torres JL, Medina I. Influence of the Degree of Unsaturation in Fish Oil Supplements on Oxidative Stress and Protein Carbonylation in the Cerebral Cortex and Cerebellum of Healthy Rats. Antioxidants (Basel) 2024; 13:1408. [PMID: 39594550 PMCID: PMC11591239 DOI: 10.3390/antiox13111408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/08/2024] [Accepted: 11/14/2024] [Indexed: 11/28/2024] Open
Abstract
ω-3 polyunsaturated fatty acids (PUFAs) are crucial for brain structure and function, especially docosahexaenoic acid (DHA). However, an excess of DHA may increase lipid peroxidation due to its high degree of unsaturation, particularly in tissues highly susceptible to oxidative stress, such as the brain. Therefore, this study evaluated the effects of 10 weeks of dietary supplementation with fish oil containing 80% DHA on oxidative stress and the modulation of the carbonylated proteome in both the cerebral cortex and cerebellum of male Sprague Dawley rats. The results were compared with those induced by oils with a lower degree of fat unsaturation (fish oil containing 25% DHA and 25% eicosapentaenoic acid, soybean oil containing 50% linoleic acid and coconut oil containing 90% saturated fat). The results demonstrated that fish oil containing 80% DHA significantly increased the ω3/ω6 ratio in both the cortex and cerebellum while stimulating antioxidant defense by enhancing the reduced glutathione amount and decreasing the carbonylation of specific proteins, mainly those involved in glycolysis and neurotransmission. The majority of sensitive proteins in both brain regions followed this carbonylation trend (in decreasing order): soybean > EPA/DHA 1:1 > coconut > 80% DHA. The results also indicated that the cerebellum is more responsive than the cortex to changes in the cellular redox environment induced by varying degrees of fat unsaturation. In conclusion, under healthy conditions, dietary supplementation with fish oils containing high DHA levels makes the brain more resilient to potential oxidative insults compared to oils with lower DHA content and a lower degree of fatty acid unsaturation.
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Affiliation(s)
- Francisco Moreno
- Institute of Marine Research—Spanish National Research Council (IIM-CSIC), Eduardo Cabello 6, 36208 Vigo, Spain; (F.M.); (I.F.); (B.M.-P.); (I.M.)
- University of Vigo, Circunvalación ao Campus Universitario, 36310 Vigo, Spain
| | - Lucía Méndez
- Institute of Marine Research—Spanish National Research Council (IIM-CSIC), Eduardo Cabello 6, 36208 Vigo, Spain; (F.M.); (I.F.); (B.M.-P.); (I.M.)
| | - Ingrid Fernández
- Institute of Marine Research—Spanish National Research Council (IIM-CSIC), Eduardo Cabello 6, 36208 Vigo, Spain; (F.M.); (I.F.); (B.M.-P.); (I.M.)
| | - Bernat Miralles-Pérez
- Institute of Marine Research—Spanish National Research Council (IIM-CSIC), Eduardo Cabello 6, 36208 Vigo, Spain; (F.M.); (I.F.); (B.M.-P.); (I.M.)
- Pharmacology Unit, Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Sant Llorenç 21, 43201 Reus, Spain; (M.G.); (M.R.)
| | - Montserrat Giralt
- Pharmacology Unit, Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Sant Llorenç 21, 43201 Reus, Spain; (M.G.); (M.R.)
| | - Marta Romeu
- Pharmacology Unit, Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Sant Llorenç 21, 43201 Reus, Spain; (M.G.); (M.R.)
| | - Sara Ramos-Romero
- Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Av. Diagonal 643, 08028 Barcelona, Spain;
- Nutrition & Food Safety Research Institute (INSA-UB), Maria de Maeztu Unit of Excellence, Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain;
- Institute of Advanced Chemistry of Catalonia—Spanish National Research Council (IQAC-CSIC), Jordi Girona 18-26, 08034 Barcelona, Spain
| | - Josep Lluís Torres
- Nutrition & Food Safety Research Institute (INSA-UB), Maria de Maeztu Unit of Excellence, Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain;
- Institute of Advanced Chemistry of Catalonia—Spanish National Research Council (IQAC-CSIC), Jordi Girona 18-26, 08034 Barcelona, Spain
| | - Isabel Medina
- Institute of Marine Research—Spanish National Research Council (IIM-CSIC), Eduardo Cabello 6, 36208 Vigo, Spain; (F.M.); (I.F.); (B.M.-P.); (I.M.)
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Hanie MH, Mohammad Reza A, Mansoureh S, Fatemeh SB, Ali S. Exploring the impact of melatonin and omega-3, individually and in combination, on cognitive function, histological changes, and oxidant-antioxidant balance in male rats with dorsal CA1 hippocampal lesions. Brain Res 2024; 1840:149046. [PMID: 38821333 DOI: 10.1016/j.brainres.2024.149046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 05/19/2024] [Accepted: 05/28/2024] [Indexed: 06/02/2024]
Abstract
BACKGROUND AND OBJECTIVE Damage to the hippocampus leads to increased anxiety, memory problems, and learning disabilities. Melatonin (MLT), a hormone secreted by the pineal gland, serves as an antioxidant and provides defense against nerve damage. Omega-3 (ω3) is known for improving brain function. This study aims to examine the impact of melatonin and omega-3, both individually and in combination, on cognitive function, histological changes, and the balance between oxidants and antioxidants in male rats with injuries to the dorsal CA1 hippocampus. MATERIAL AND METHODS Five rat groups (n = 8) were examined. The sham group was given normal saline via intraperitoneal (ip) and gavage routes. After a local lesion in the hippocampus, the lesion group underwent the same treatment. The MLT group was given melatonin (10 mg/kg, ip), the ω3 group was provided with omega-3 (0.8 g/kg, gavage), and the MLT + ω3 group received both treatments. Injections were administered every other day for 10 days. On the 11th day, behavioral assessments were conducted, and then pyramidal cells were quantified using image analysis software. Serum samples were assessed for levels of oxidants and antioxidants. RESULTS The results from the open field test indicated a significant increase in distance moved in the Lesion + MLT + ω3 group compared to the lesion group (P < 0.05). Performance in the novel object recognition test showed improvement in the ω3 and MLT + ω3 treated groups compared to the lesion group (P < 0.05). Additionally, social interaction duration notably increased in the ω3, MLT, and MLT + ω3 treated groups compared to the lesion group. The number of degenerated cells in the CA1, CA2, and CA3 areas of the lesion group significantly increased compared to the sham group, but melatonin and omega-3 notably reduced this number (P < 0.05). The serum levels of the antioxidant enzymes,include superoxide dismutase, glutathione peroxidase, and catalase in the lesion group notably changed compared to the sham group, but omega-3 effectively restored them to control levels. CONCLUSION According to increase in distance moved, memory function, learning and social interactions of the animal in the behavioral results and the reduction of degenerate cells in the histological results, it can be said that these effects may be part of the neuroprotective effects of melatonin and omega-3. The increase in levels of antioxidant enzymes, particularly omega-3, indicates their promise as therapeutic agents for reducing oxidative stress-induced damage in neurological disorders.
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Affiliation(s)
- Mahmoudi Hashemi Hanie
- Department of Anatomy, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Afarinesh Mohammad Reza
- Neuroscience Research Center, Institute of Neuropharmachology, Kerman University of Medical Sciences, Kerman, Iran; Cognitive Neuroscience Research Center, Institute of Neuropharmachology, Kerman University of Medical Sciences, Kerman, Iran.
| | - Sabzalizadeh Mansoureh
- Neuroscience Research Center, Institute of Neuropharmachology, Kerman University of Medical Sciences, Kerman, Iran; Cognitive Neuroscience Research Center, Institute of Neuropharmachology, Kerman University of Medical Sciences, Kerman, Iran
| | - Sheikh Bahaei Fatemeh
- Department of Anatomy, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Shamsara Ali
- Department of Anatomy, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran; Neuroscience Research Center, Institute of Neuropharmachology, Kerman University of Medical Sciences, Kerman, Iran.
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Adiguzel E, Bozkurt NM, Unal G. Independent and combined effects of astaxanthin and omega-3 on behavioral deficits and molecular changes in a prenatal valproic acid model of autism in rats. Nutr Neurosci 2024; 27:590-606. [PMID: 37534957 DOI: 10.1080/1028415x.2023.2239575] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2023]
Abstract
Objectives: Autism is a devastating neurodevelopmental disorder and recent studies showed that omega-3 or astaxanthin might reduce autistic symptoms due to their anti-inflammatory properties. Therefore, we investigated the effects of omega-3 and astaxanthin on the VPA-induced autism model of rats.Material and Methods: Female Wistar albino pups (n = 40) were grouped as control, autistic, astaxanthin (2 mg/kg), omega-3 (200 mg/kg), and astaxanthin (2 mg/kg)+omega-3 (200 mg/kg). All groups except the control were prenatally exposed to VPA. Astaxanthin and omega-3 were orally administered from the postnatal day 41 to 68 and behavioral tests were performed between day 69 and 73. The rats were decapitated 24 h after the behavioral tests and hippocampal and prefrontal cytokines and 5-HT levels were analyzed by ELISA.Results: VPA rats have increased grooming behavior while decreased sociability (SI), social preference index (SPI), discrimination index (DI), and prepulse inhibition (PPI) compared to control. Additionally, IL-1β, IL-6, TNF-α, and IFN-γ levels increased while IL-10 and 5-HT levels decreased in both brain regions. Astaxanthin treatment raised SI, SPI, DI, PPI, and prefrontal IL-10 levels. It also raised 5-HT levels and decreased IL-6 levels in both brain regions. Omega-3 and astaxanthin + omega-3 increased the SI, SPI, DI, and PPI and decreased grooming behavior. Moreover, they increased IL-10 and 5-HT levels whereas decreased IL-1β, IL-6, TNF-α, IFN-γ levels in both brain regions.Conclusions: Our results showed that VPA administration mimicked the behavioral and molecular changes of autism in rats. Single and combined administration of astaxanthin and omega-3 improved the autistic-like behavioral and molecular changes in the VPA model of rats.
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Affiliation(s)
- Emre Adiguzel
- Faculty of Health Sciences, Department of Nutrition and Dietetics, Karamanoğlu Mehmetbey University, Karaman, Türkiye
| | - Nuh Mehmet Bozkurt
- Faculty of Pharmacy, Department of Pharmacology, Erciyes University, Kayseri, Türkiye
- Experimental Research and Application Center (DEKAM), Brain Research Unit, Erciyes University, Kayseri, Türkiye
- e-Neuro Lab, Drug Application and Research Center (ERFARMA), Erciyes University, Kayseri, Türkiye
| | - Gokhan Unal
- Faculty of Pharmacy, Department of Pharmacology, Erciyes University, Kayseri, Türkiye
- Experimental Research and Application Center (DEKAM), Brain Research Unit, Erciyes University, Kayseri, Türkiye
- e-Neuro Lab, Drug Application and Research Center (ERFARMA), Erciyes University, Kayseri, Türkiye
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Moreno F, Méndez L, Raner A, Miralles-Pérez B, Romeu M, Ramos-Romero S, Torres JL, Medina I. Dietary Marine Oils Selectively Decrease Obesogenic Diet-Derived Carbonylation in Proteins Involved in ATP Homeostasis and Glutamate Metabolism in the Rat Cerebellum. Antioxidants (Basel) 2024; 13:103. [PMID: 38247527 PMCID: PMC10812471 DOI: 10.3390/antiox13010103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 01/06/2024] [Accepted: 01/12/2024] [Indexed: 01/23/2024] Open
Abstract
The regular intake of diets high in saturated fat and sugars increases oxidative stress and has been linked to cognitive decline and premature brain aging. The cerebellum is highly vulnerable to oxidative stress and thus, obesogenic diets might be particularly detrimental to this tissue. However, the precise molecular mechanisms behind obesity-related brain damage are still not clear. Since protein carbonylation, a biomarker of oxidative stress, influences protein functions and is involved in metabolic control, the current investigation addressed the effect of long-term high-fat and high-sucrose diet intake on the cerebellum of Sprague-Dawley rats by deciphering the changes caused in the carbonylated proteome. The antioxidant effects of fish oil supplementation on cerebellar carbonylated proteins were also investigated. Lipid peroxidation products and carbonylated proteins were identified and quantified using immunoassays and 2D-LC-MS/MS in the cerebellum. After 21 weeks of nutritional intervention, the obesogenic diet selectively increased carbonylation of the proteins that participate in ATP homeostasis and glutamate metabolism in the cerebellum. Moreover, the data demonstrated that fish oil supplementation restrained carbonylation of the main protein targets oxidatively damaged by the obesogenic diet, and additionally protected against carbonylation of several other proteins involved in amino acid biosynthesis and neurotransmission. Therefore, dietary interventions with fish oils could help the cerebellum to be more resilient to oxidative damage. The results could shed some light on the effect of high-fat and high-sucrose diets on redox homeostasis in the cerebellum and boost the development of antioxidant-based nutritional interventions to improve cerebellum health.
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Affiliation(s)
- Francisco Moreno
- Instituto de Investigaciones Marinas—Consejo Superior de Investigaciones Científicas (IIM-CSIC), Eduardo Cabello 6, E-36208 Vigo, Spain; (F.M.); (A.R.); (I.M.)
- Universidad de Vigo, Circunvalación ao Campus Universitario, E-36310 Vigo, Spain
| | - Lucía Méndez
- Instituto de Investigaciones Marinas—Consejo Superior de Investigaciones Científicas (IIM-CSIC), Eduardo Cabello 6, E-36208 Vigo, Spain; (F.M.); (A.R.); (I.M.)
| | - Ana Raner
- Instituto de Investigaciones Marinas—Consejo Superior de Investigaciones Científicas (IIM-CSIC), Eduardo Cabello 6, E-36208 Vigo, Spain; (F.M.); (A.R.); (I.M.)
| | - Bernat Miralles-Pérez
- Unidad de Farmacología, Facultad de Medicina y Ciencias de la Salud, Universidad Rovira i Virgili, Sant Llorenç 21, E-43201 Reus, Spain; (B.M.-P.); (M.R.)
| | - Marta Romeu
- Unidad de Farmacología, Facultad de Medicina y Ciencias de la Salud, Universidad Rovira i Virgili, Sant Llorenç 21, E-43201 Reus, Spain; (B.M.-P.); (M.R.)
| | - Sara Ramos-Romero
- Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Av Diagonal 643, E-08028 Barcelona, Spain;
- Nutrition & Food Safety Research Institute (INSA-UB), Maria de Maeztu Unit of Excellence, E-08921 Santa Coloma de Gramenet, Spain;
- Instituto de Química Avanzada de Catalunya—Consejo Superior de Investigaciones Científicas (IQAC-CSIC), Jordi Girona 18-26, E-08034 Barcelona, Spain
| | - Josep Lluís Torres
- Nutrition & Food Safety Research Institute (INSA-UB), Maria de Maeztu Unit of Excellence, E-08921 Santa Coloma de Gramenet, Spain;
- Instituto de Química Avanzada de Catalunya—Consejo Superior de Investigaciones Científicas (IQAC-CSIC), Jordi Girona 18-26, E-08034 Barcelona, Spain
| | - Isabel Medina
- Instituto de Investigaciones Marinas—Consejo Superior de Investigaciones Científicas (IIM-CSIC), Eduardo Cabello 6, E-36208 Vigo, Spain; (F.M.); (A.R.); (I.M.)
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Moreno F, Méndez L, Raner A, Miralles-Pérez B, Romeu M, Ramos-Romero S, Torres JL, Medina I. Fish oil supplementation counteracts the effect of high-fat and high-sucrose diets on the carbonylated proteome in the rat cerebral cortex. Biomed Pharmacother 2023; 168:115708. [PMID: 37857255 DOI: 10.1016/j.biopha.2023.115708] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 10/03/2023] [Accepted: 10/11/2023] [Indexed: 10/21/2023] Open
Abstract
High daily intake of saturated fats and refined carbohydrates, which often leads to obesity and overweight, has been associated with cognitive impairment, premature brain aging and the aggravation of neurodegenerative diseases. Although the molecular pathology of obesity-related brain damage is not fully understood, the increased levels of oxidative stress induced by the diet seem to be definitively involved. Being protein carbonylation determinant for protein activity and function and a main consequence of oxidative stress, this study aims to investigate the effect of the long-term high-fat and sucrose diet intake on carbonylated proteome of the cerebral cortex of Sprague-Dawley rats. To achieve this goal, the study identified and quantified the carbonylated proteins and lipid peroxidation products in the cortex, and correlated them with biometrical, biochemical and other redox status parameters. Results demonstrated that the obesogenic diet selectively increased oxidative damage of specific proteins that participate in fundamental pathways for brain function, i.e. energy production, glucose metabolism and neurotransmission. This study also evaluated the antioxidant properties of fish oil to counteract diet-induced brain oxidative damage. Fish oil supplementation demonstrated a stronger capacity to modulate carbonylated proteome in the brain cortex. Data indicated that fish oils did not just decrease carbonylation of proteins affected by the obesogenic diet, but also decreased the oxidative damage of other proteins participating in the same metabolic functions, reinforcing the beneficial effect of the supplement on those pathways. The results could help contribute to the development of successful nutritional-based interventions to prevent cognitive decline and promote brain health.
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Affiliation(s)
- Francisco Moreno
- Instituto de Investigaciones Marinas - Consejo Superior de Investigaciones Científicas (IIM-CSIC), Eduardo Cabello 6, E-36208 Vigo, Galicia, Spain; Universidad de Vigo, Spain
| | - Lucía Méndez
- Instituto de Investigaciones Marinas - Consejo Superior de Investigaciones Científicas (IIM-CSIC), Eduardo Cabello 6, E-36208 Vigo, Galicia, Spain.
| | - Ana Raner
- Instituto de Investigaciones Marinas - Consejo Superior de Investigaciones Científicas (IIM-CSIC), Eduardo Cabello 6, E-36208 Vigo, Galicia, Spain
| | - Bernat Miralles-Pérez
- Unidad de Farmacología, Facultad de Medicina y Ciencias de la Salud, Universidad Rovira i Virgili, Sant Llorenç 21, E-43201 Reus, Spain
| | - Marta Romeu
- Unidad de Farmacología, Facultad de Medicina y Ciencias de la Salud, Universidad Rovira i Virgili, Sant Llorenç 21, E-43201 Reus, Spain
| | - Sara Ramos-Romero
- Faculty of Biology, University of Barcelona, Av Diagonal 643, E-08028 Barcelona, Spain; Department of Cell Biology, Physiology and Immunology, Av Diagonal 643, E-08028 Barcelona, Spain; Nutrition & Food Safety Research Institute (INSA-UB), Maria de Maeztu Unit of Excellence, E-08921 Santa Coloma De Gramenet, Spain; Instituto de Química Avanzada de Catalunya - Consejo Superior de Investigaciones Científicas (IQAC-CSIC), Jordi Girona 18-26, E-08034 Barcelona, Spain
| | - Josep Lluís Torres
- Nutrition & Food Safety Research Institute (INSA-UB), Maria de Maeztu Unit of Excellence, E-08921 Santa Coloma De Gramenet, Spain; Instituto de Química Avanzada de Catalunya - Consejo Superior de Investigaciones Científicas (IQAC-CSIC), Jordi Girona 18-26, E-08034 Barcelona, Spain
| | - Isabel Medina
- Instituto de Investigaciones Marinas - Consejo Superior de Investigaciones Científicas (IIM-CSIC), Eduardo Cabello 6, E-36208 Vigo, Galicia, Spain
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Ebrahimi M, Ahangar N, Zamani E, Shaki F. L-Carnitine Prevents Behavioural Alterations in Ketamine-Induced Schizophrenia in Mice: Possible Involvement of Oxidative Stress and Inflammation Pathways. J Toxicol 2023; 2023:9093231. [PMID: 37363159 PMCID: PMC10289879 DOI: 10.1155/2023/9093231] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 01/10/2023] [Accepted: 06/07/2023] [Indexed: 06/28/2023] Open
Abstract
Schizophrenia is a chronic mental complaint known as cognitive impairment. There has been evidence that inflammation and oxidative stress play a main role in schizophrenia pathophysiology. This study aimed to investigate the effects of l-carnitine, as a potent antioxidant, on the treatment of behavioural and biochemical disturbances in mice with ketamine-induced schizophrenia. In this study, schizophrenia was induced in mice by ketamine (25 mg/kg/day, i.p). Before induction of schizophrenia, mice were treated with l-carnitine (100, 200, and 400 mg/kg/day, i.p). Then, behavioural impairments were evaluated by open field (OF) assessment and social interaction test (SIT). After brain tissue isolation, reactive oxygen species (ROS), glutathione concentration (GSH), lipid peroxidation (LPO), protein carbonyl oxidation, superoxide dismutase activity (SOD), and glutathione peroxidase activity (GPx) were assessed as oxidative stress markers. Furthermore, inflammatory biomarkers such as tumour necrosis factor alpha (TNF-α) and nitric oxide (NO) were evaluated in brain tissue. Our results showed ketamine increased inflammation and oxidative damage in brain tissue that was similar to behaviour disorders in mice. Interestingly, l-carnitine significantly decreased oxidative stress and inflammatory markers compared with ketamine-treated mice. In addition, l-carnitine prevented and reversed ketamine-induced alterations in the activities of SOD and GPx enzymes in mice's brains. Also, improved performance in OFT (locomotor activity test) and SIT was observed in l-carnitine-treated mice. These data provided evidence that, due to the antioxidant and anti-inflammatory effects of l-carnitine, it has a neuroprotective effect on mice model of schizophrenia.
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Affiliation(s)
- Mehrasa Ebrahimi
- Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
- Students Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
| | - Nematollah Ahangar
- Department of Pharmacology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Ehsan Zamani
- Department of Pharmacology and Toxicology, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran
| | - Fatemeh Shaki
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
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Nolan SO, Hodges SL, Binder MS, Smith GD, Okoh JT, Jefferson TS, Escobar B, Lugo JN. Dietary rescue of adult behavioral deficits in the Fmr1 knockout mouse. PLoS One 2022; 17:e0262916. [PMID: 35089938 PMCID: PMC8797197 DOI: 10.1371/journal.pone.0262916] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 01/09/2022] [Indexed: 11/21/2022] Open
Abstract
The current study aimed to further address important questions regarding the therapeutic efficacy of omega-3 fatty acids for various behavioral and neuroimmune aspects of the Fmr1 phenotype. To address these questions, our experimental design utilized two different omega-3 fatty acid administration timepoints, compared to both standard laboratory chow controls ("Standard") and a diet controlling for the increase in fat content ("Control Fat"). In the first paradigm, post-weaning supplementation (after postnatal day 21) with the omega-3 fatty acid diet ("Omega-3") reversed deficits in startle threshold, but not deficits in prepulse inhibition, and the effect on startle threshold was not specific to the Omega-3 diet. However, post-weaning supplementation with both experimental diets also impaired acquisition of a fear response, recall of the fear memory and contextual fear conditioning compared to the Standard diet. The post-weaning Omega-3 diet reduced hippocampal expression of IL-6 and this reduction of IL-6 was significantly associated with diminished performance in the fear conditioning task. In the perinatal experimental paradigm, the Omega-3 diet attenuated hyperactivity and acquisition of a fear response. Additionally, perinatal exposure to the Control Fat diet (similar to a "Western" diet) further diminished nonsocial anxiety in the Fmr1 knockout. This study provides significant evidence that dietary fatty acids throughout the lifespan can significantly impact the behavioral and neuroimmune phenotype of the Fmr1 knockout model.
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Affiliation(s)
- Suzanne O. Nolan
- Department of Psychology and Neuroscience, Baylor University, Waco, Texas, United States of America
| | - Samantha L. Hodges
- Institute of Biomedical Studies, Baylor University, Waco, Texas, United States of America
| | - Matthew S. Binder
- Department of Psychology and Neuroscience, Baylor University, Waco, Texas, United States of America
| | - Gregory D. Smith
- Institute of Biomedical Studies, Baylor University, Waco, Texas, United States of America
| | - James T. Okoh
- Department of Psychology and Neuroscience, Baylor University, Waco, Texas, United States of America
| | - Taylor S. Jefferson
- Department of Psychology and Neuroscience, Baylor University, Waco, Texas, United States of America
| | - Brianna Escobar
- Department of Psychology and Neuroscience, Baylor University, Waco, Texas, United States of America
| | - Joaquin N. Lugo
- Department of Psychology and Neuroscience, Baylor University, Waco, Texas, United States of America
- Institute of Biomedical Studies, Baylor University, Waco, Texas, United States of America
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Onaolapo OJ, Onaolapo AY. Nutrition, nutritional deficiencies, and schizophrenia: An association worthy of constant reassessment. World J Clin Cases 2021; 9:8295-8311. [PMID: 34754840 PMCID: PMC8554424 DOI: 10.12998/wjcc.v9.i28.8295] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 05/04/2021] [Accepted: 08/10/2021] [Indexed: 02/06/2023] Open
Abstract
Schizophrenia is a mental health disorder that occurs worldwide, cutting across cultures, socioeconomic groups, and geographical barriers. Understanding the details of the neurochemical basis of schizophrenia, factors that contribute to it and possible measures for intervention are areas of ongoing research. However, what has become more evident is the fact that in targeting the neurochemical imbalances that may underlie schizophrenia, the type of response seen with currently available phamacotherapeutic agents does not provide all the answers that are needed. Therefore, the possible contribution of non-pharmacological approaches to schizophrenia management is worthy of consideration. In recent times, research is beginning to show nutrition may play a possibly significant role in schizophrenia, affecting its development, progression and management; however, while attempts had been made to examine this possible relationship from different angles, articles addressing it from a holistic point of view are not common. In this review, we examine existing scientific literature dealing with the possible relationship between nutrition and schizophrenia, with a view to elucidating the impact of diet, nutritional deficiencies and excesses on the aetiology, progression, management and outcome of schizophrenia. Secondly, the effect of nutritional supplements in prevention, as sole therapy, or adjuncts in schizophrenia management are examined.
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Affiliation(s)
- Olakunle James Onaolapo
- Behavioural Neuroscience/Neuropharmacology Unit, Department of Pharmacology, Ladoke Akintola University of Technology, Osun State 234, Nigeria
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Shared Biological Pathways between Antipsychotics and Omega-3 Fatty Acids: A Key Feature for Schizophrenia Preventive Treatment? Int J Mol Sci 2021; 22:ijms22136881. [PMID: 34206945 PMCID: PMC8269187 DOI: 10.3390/ijms22136881] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 06/18/2021] [Accepted: 06/23/2021] [Indexed: 12/25/2022] Open
Abstract
Schizophrenia typically emerges during adolescence, with progression from an ultra-high risk state (UHR) to the first episode of psychosis (FEP) followed by a chronic phase. The detailed pathophysiology of schizophrenia and the factors leading to progression across these stages remain relatively unknown. The current treatment relies on antipsychotics, which are effective for FEP and chronic schizophrenia but ineffective for UHR patients. Antipsychotics modulate dopaminergic and glutamatergic neurotransmission, inflammation, oxidative stress, and membrane lipids pathways. Many of these biological pathways intercommunicate and play a role in schizophrenia pathophysiology. In this context, research of preventive treatment in early stages has explored the antipsychotic effects of omega-3 supplementation in UHR and FEP patients. This review summarizes the action of omega-3 in various biological systems involved in schizophrenia. Similar to antipsychotics, omega-3 supplementation reduces inflammation and oxidative stress, improves myelination, modifies the properties of cell membranes, and influences dopamine and glutamate pathways. Omega-3 supplementation also modulates one-carbon metabolism, the endocannabinoid system, and appears to present neuroprotective properties. Omega-3 has little side effects compared to antipsychotics and may be safely prescribed for UHR patients and as an add-on for FEP patients. This could to lead to more efficacious individualised treatments, thus contributing to precision medicine in psychiatry.
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10
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Casquero-Veiga M, Romero-Miguel D, MacDowell KS, Torres-Sanchez S, Garcia-Partida JA, Lamanna-Rama N, Gómez-Rangel V, Romero-Miranda A, Berrocoso E, Leza JC, Arango C, Desco M, Soto-Montenegro ML. Omega-3 fatty acids during adolescence prevent schizophrenia-related behavioural deficits: Neurophysiological evidences from the prenatal viral infection with PolyI:C. Eur Neuropsychopharmacol 2021; 46:14-27. [PMID: 33735708 DOI: 10.1016/j.euroneuro.2021.02.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 01/11/2021] [Accepted: 02/09/2021] [Indexed: 12/20/2022]
Abstract
The likely involvement of inflammation and oxidative stress (IOS) in mental disease has led to advocate anti-oxidant and anti-inflammatory drugs as therapeutic strategies in the treatment of schizophrenia. Since omega-3 fatty acids (ω-3) show anti-inflammatory/neuroprotective properties, we aim to evaluate whether ω-3 treatment during adolescence in the maternal immune stimulation (MIS) animal model of schizophrenia could prevent the brain and behavioural deficits described in adulthood. At gestational day 15, PolyI:C (4 mg/kg) or saline (VH) were injected to pregnant Wistar rats. Male offspring received ω-3 (800 mg/kg) or saline (Sal) daily from postnatal day (PND) 35-49, defining 4 groups: MIS-ω-3; MIS-Sal; VH-ω-3 and VH-Sal. At PND70, rats were submitted to prepulse inhibition test (PPI). FDG-PET and T2-weighted MRI brain studies were performed in adulthood and analyzed by means of SPM12. IOS markers were measured in selected brain areas. MIS-offspring showed a PPI deficit compared with VH-offspring and ω-3 treatment prevented this deficit. Also, ω-3 reduced the brain metabolism in the deep mesencephalic area and prevented the volumetric abnormalities in the hippocampus but not in the ventricles in MIS-offspring. Besides, ω-3 reduced the expression of iNOS and Keap1 and increased the activity/concentration of HO1, NQO1 and GPX. Our study demonstrates that administration of ω-3 during adolescence prevents PPI behavioural deficits and hippocampal volumetric abnormalities, and partially counteracts IOS deficits via iNOS and Nrf2-ARE pathways in the MIS model. This study highlights the need for novel strategies based on anti-inflammatory/anti-oxidant compounds to alter the disease course in high-risk populations at early stages.
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Affiliation(s)
- Marta Casquero-Veiga
- Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; CIBER de Salud Mental (CIBERSAM), Madrid, Spain
| | | | - Karina S MacDowell
- CIBER de Salud Mental (CIBERSAM), Madrid, Spain; Department of Pharmacology & Toxicology, School of Medicine, University Complutense (UCM), IIS Imas12, IUIN, Madrid, Spain
| | - Sonia Torres-Sanchez
- CIBER de Salud Mental (CIBERSAM), Madrid, Spain; Neuropsychopharmacology & Psychobiology Research Group, Psychobiology Area, Department of Psychology, University of Cádiz, Puerto Real (Cádiz), Spain; Instituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz, INiBICA, Hospital Universitario Puerta del Mar, Cádiz, Spain
| | - Jose Antonio Garcia-Partida
- CIBER de Salud Mental (CIBERSAM), Madrid, Spain; Instituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz, INiBICA, Hospital Universitario Puerta del Mar, Cádiz, Spain; Neuropsychopharmacology & Psychobiology Research Group, Department of Neuroscience, University of Cádiz, Cádiz, Spain
| | | | | | | | - Esther Berrocoso
- CIBER de Salud Mental (CIBERSAM), Madrid, Spain; Neuropsychopharmacology & Psychobiology Research Group, Psychobiology Area, Department of Psychology, University of Cádiz, Puerto Real (Cádiz), Spain; Instituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz, INiBICA, Hospital Universitario Puerta del Mar, Cádiz, Spain
| | - Juan C Leza
- CIBER de Salud Mental (CIBERSAM), Madrid, Spain; Department of Pharmacology & Toxicology, School of Medicine, University Complutense (UCM), IIS Imas12, IUIN, Madrid, Spain
| | - Celso Arango
- CIBER de Salud Mental (CIBERSAM), Madrid, Spain; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - Manuel Desco
- Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; CIBER de Salud Mental (CIBERSAM), Madrid, Spain; Departamento of Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Leganés, Spain; Centro Nacional de Investigaciones Cardiovasculares, CNIC, Madrid, Spain.
| | - María Luisa Soto-Montenegro
- Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; CIBER de Salud Mental (CIBERSAM), Madrid, Spain.
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11
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Cao T, Tang M, Jiang P, Zhang B, Wu X, Chen Q, Zeng C, Li N, Zhang S, Cai H. A Potential Mechanism Underlying the Therapeutic Effects of Progesterone and Allopregnanolone on Ketamine-Induced Cognitive Deficits. Front Pharmacol 2021; 12:612083. [PMID: 33767621 PMCID: PMC7985688 DOI: 10.3389/fphar.2021.612083] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 01/29/2021] [Indexed: 11/13/2022] Open
Abstract
Ketamine exposure can model cognitive deficits associated with schizophrenia. Progesterone (PROG) and its active metabolite allopregnanolone (ALLO) have neuroprotective effects and the pathway involving progesterone receptor membrane component 1 (PGRMC1), epidermal growth factor receptor (EGFR), glucagon-like peptide-1 receptor (GLP-1R), phosphatidylinositol 3 kinase (PI3K), and protein kinase B (Akt) appears to play a key role in their neuroprotection. The present study aimed to investigate the effects of PROG (8,16 mg kg−1) and ALLO (8,16 mg kg−1) on the reversal of cognitive deficits induced by ketamine (30 mg kg−1) via the PGRMC1 pathway in rat brains, including hippocampus and prefrontal cortex (PFC). Cognitive performance was evaluated by Morris water maze (MWM) test. Western blot and real-time quantitative polymerase chain reaction were utilized to assess the expression changes of protein and mRNA. Additionally, concentrations of PROG and ALLO in plasma, hippocampus and PFC were measured by a liquid chromatography-tandem mass spectrometry method. We demonstrated that PROG or ALLO could reverse the impaired spatial learning and memory abilities induced by ketamine, accompanied with the upregulation of PGRMC1/EGFR/GLP-1R/PI3K/Akt pathway. Additionally, the coadministration of AG205 abolished their neuroprotective effects and induced cognitive deficits similar with ketamine. More importantly, PROG concentrations were markedly elevated in PROG-treated groups in hippocampus, PFC and plasma, so as for ALLO concentrations in ALLO-treated groups. Interestingly, ALLO (16 mg kg−1) significantly increased the levels of PROG. These findings suggest that PROG can exert its neuroprotective effects via activating the PGRMC1/EGFR/GLP-1R/PI3K/Akt pathway in the brain, whereas ALLO also restores cognitive deficits partially via increasing the level of PROG in the brain to activate the PGRMC1 pathway.
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Affiliation(s)
- Ting Cao
- Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China
| | - MiMi Tang
- Department of Pharmacy, Xiangya Hospital of Central South University, Changsha, China.,Institute of Hospital Pharmacy, Xiangya Hospital, Central South University, Changsha, China
| | - Pei Jiang
- Institute of Clinical Pharmacology, Jining First People's Hospital, Jining Medical University, Jining, China
| | - BiKui Zhang
- Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China
| | - XiangXin Wu
- Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China
| | - Qian Chen
- Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China
| | - CuiRong Zeng
- Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China
| | - NaNa Li
- Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China
| | - ShuangYang Zhang
- Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China
| | - HuaLin Cai
- Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China
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12
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da Costa AEM, Gomes NS, Gadelha Filho CVJ, Linhares MGOES, da Costa RO, Chaves Filho AJM, Cordeiro RC, Vasconcelos GS, da Silva FER, Araujo TDS, Vasconcelos SMM, Lucena DF, Macêdo DS. Sex influences in the preventive effects of peripubertal supplementation with N-3 polyunsaturated fatty acids in mice exposed to the two-hit model of schizophrenia. Eur J Pharmacol 2021; 897:173949. [PMID: 33607108 DOI: 10.1016/j.ejphar.2021.173949] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 01/30/2021] [Accepted: 02/11/2021] [Indexed: 01/05/2023]
Abstract
Schizophrenia is a devastating neurodevelopmental disorder. The animal model based on perinatal immune activation, as first-hit, combined with peripubertal stress, as a second hit, has gained evidence in recent years. Omega-3 polyunsaturated fatty acids (n3-PUFAs) is being a promise for schizophrenia prevention. Nevertheless, the influence of sex in schizophrenia neurobiology and prevention has been neglected. Thus, the present study evaluates the preventive effects of n3-PUFAs in both sexes' mice submitted to the two-hit model and the participation of oxidative changes in this mechanism. The two-hit consisted of polyI:C administration from postnatal days (PNs) 5-7, and unpredictable stress from PNs35-43. n3-PUFAs were administered from PNs30-60. Prepulse inhibition of the startle reflex (PPI), social interaction, and Y-maze tests were conducted between PNs70-72 to evaluate positive-, negative-, and cognitive-like schizophrenia symptoms. We assessed brain oxidative changes in brain areas and plasma. Both sexes' two-hit mice presented deficits in PPI, social interaction, and working memory that were prevented by n3-PUFAs. In two-hit females, n3-PUFAs prevented increments in nitrite levels in the prefrontal cortex (PFC), hippocampus, striatum, and plasma TBARS levels. In two-hit males, n3-PUFAs prevented the increase in TBARS in the PFC, hippocampus, and striatum. Notably, male mice that received only n3-PUFAs without hit exposure presented impairments in working memory and social interaction. These results add further preclinical evidence for n3-PUFAs as an accessible and effective alternative in preventing behavioral and oxidative changes related to schizophrenia but call attention to the need for precaution in this indication due to hit- and sex-sensitive issues.
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Affiliation(s)
- Ayane Edwiges Moura da Costa
- Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
| | - Nayana Soares Gomes
- Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
| | - Carlos Venício Jatai Gadelha Filho
- Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
| | | | - Roberta Oliveira da Costa
- Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
| | - Adriano José Maia Chaves Filho
- Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
| | - Rafaela Carneiro Cordeiro
- Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
| | - Germana Silva Vasconcelos
- Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
| | - Francisco Eliclécio Rodrigues da Silva
- Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
| | - Tatiane da Silva Araujo
- Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
| | - Silvânia Maria Mendes Vasconcelos
- Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
| | - David Freitas Lucena
- Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
| | - Danielle S Macêdo
- Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil; National Institute for Translational Medicine (INCT-TM, CNPq), Ribeirão Preto, SP, Brazil.
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13
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Ahmed MG, Ibrahim MED, El Sayed HR, Ahmed SM. Short term chronic toxicity of tributyltin on the testes of adult albino rats and the possible protective role of omega-3. Hum Exp Toxicol 2020; 40:214-230. [PMID: 32783468 DOI: 10.1177/0960327120947451] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The declining rate of male fertility is a growing concern. Tributyltin (TBT) is a well-known endocrine disruptor (ED), that induces imposex in female gastropods and is widely used in various industrial applications. The aim of this study was to evaluate the toxic effects of TBT on the testes of adult albino rats and the possible role of omega-3. Forty two adult male albino rats were divided into five groups; control group (Group I) and four experimental groups: omega-3 treated group, TBT treated group, TBT & omega-3 treated group and follow up group. At the end of the study, the rats were subjected to biochemical, histological, immunohistochemical staining for Ki-67 and seminal examinations. Our results clarfied that TBT induced a significant decrease in testosterone, FSH, LH and serum glutathione peroxidase levels and a significant increase in the serum Malondialdehyde as compared to the control group. Tributyltin induced disorganization and shrinkage of seminiferous tubules, apoptosis, cellular damage and marked reduction in the germinal epithelium. A significant decrease in the cell proliferation and arrested spermatogenesis were also detected. Seminal analysis of TBT group showed a significant affection of all parameters as compared to other groups. Omega-3 ameliorated all of these hazardous effects. Follow up group still showed toxic effects. In conclusion, TBT has a toxic effect on the testis. Increased testicular oxidative stress, cellular damage and arrest of spermatogenesis with attenuation in antioxidant defenses are all contributing factors. Omega-3 can protect against TBT induced reproductive toxicity.
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Affiliation(s)
- Marwa G Ahmed
- Department of Forensic Medicine and Clinical Toxicology, 68865Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Mona El-Demerdash Ibrahim
- Department of Forensic Medicine and Clinical Toxicology, 68865Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Hoda R El Sayed
- Department of Forensic Medicine and Clinical Toxicology, 68865Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Samah M Ahmed
- Department of Histology & Cell Biology, 68865Faculty of Medicine, Zagazig University, Zagazig, Egypt
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14
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Supp AD, Avila S, Mastella GA, Damásio L, de Oliveira IH, Godoi AK, Michels A, Schuck PF, Zugno AI. Ascorbic acid supplementation attenuates schizophrenia-like symptoms in an animal model induced by ketamine. Int J Dev Neurosci 2020; 81:26-36. [PMID: 32780510 DOI: 10.1002/jdn.10058] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 07/22/2020] [Accepted: 07/30/2020] [Indexed: 12/20/2022] Open
Abstract
Schizophrenia is a chronic neuropsychiatric disorder with a poorly understood pathophysiology. The theories about the disorder are mainly about dysregulation in one or more systems of neurotransmitters, and the progression triggers the presence of inflammatory markers indicates the possibility that the disorder is initially an inflammatory disease. The objective was to evaluate the ascorbic acid supplementation in an animal model of schizophrenia, on behavioral parameters, and cytokines involved in inflammation IL-1β, IL-10. Wistar rats with 60 days of age were used which were supplemented with ascorbic acid at 0.1, 1, and 10 mg/kg or saline for 14 days via orogastric gavage. Subsequently, four groups were given ketamine (25 mg/kg) and four groups received intraperitoneal saline from the 9th-15th day of the experiment. After 30 min of the last administration of ketamine/saline, and behavioral test, rats were killed by guillotine decapitation and the brain structures were carefully dissected for biochemical analysis. Results showed that ascorbic acid supplementation prevented motor sensory loss but nor alter other parameters evaluated. We concluded that ascorbic acid may be used as a therapeutic adjuvant in schizophrenia and may help to improve the schizophrenic patient's life quality.
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Affiliation(s)
- Angelo D Supp
- Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
| | - Silvio Avila
- Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
| | - Gustavo A Mastella
- Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
| | - Louyse Damásio
- Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
| | - Isabela H de Oliveira
- Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
| | - Amanda K Godoi
- Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
| | - Alander Michels
- Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
| | - Patricia F Schuck
- School of Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Alexandra I Zugno
- Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
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15
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Frajerman A, Kebir O, Chaumette B, Tessier C, Lamazière A, Nuss P, Krebs MO. [Membrane lipids in schizophrenia and early phases of psychosis: Potential biomarkers and therapeutic targets?]. Encephale 2020; 46:209-216. [PMID: 32151446 DOI: 10.1016/j.encep.2019.11.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 11/22/2019] [Accepted: 11/28/2019] [Indexed: 01/02/2023]
Abstract
The various roles of membrane lipids in human health has urged researchers to study their impact in neuropsychiatric diseases, especially in schizophrenia spectrum disorders and more recently in early stages of psychosis. The progress in mass spectrometry technologies now allows a more comprehensive analysis of phospholipids (PL) and their fatty acid (FA) molecular species. FA are defined by a carbon chain of variable length and are said to be unsaturated when their chain has one or more carbon-carbon double bonds. The PL are composed of a hydrophilic polar head with a phosphoric acid group and an hydrophobic part with FAs; they encompass glycerophospholipids and sphingolipids. The plasma membrane is a complex and dynamic structure consisting of a lipid bilayer composed of an outer layer and an inner layer of specific lipid composition. The permanent remodeling of membrane lipids involves phospholipases especially the phospholipase A2. Seventy percent of the brain consists of lipids from different classes and molecular species. Most of the brain lipids are composed of polyunsaturated fatty acid (PUFA)-enriched diacyl classes where omega-3 and omega-6 molecular species predominate. The balance between omega-3 and omega-6 is important for the neurodevelopment. PUFA are also involved in neurogenesis and neurotransmission. Sphingomyelin (SM) is a sphingolipid that influences inflammation, cell proliferation and lipid rafts formation. It is an important component of myelin sheaths of white matter and therefore is involved in cerebral connectivity. In rat models, deficiency in omega-3 causes abnormalities in dopaminergic neurotransmission, impacts on the functioning of some receptors (including cannabinoids CB1, glutamatergic N-methyl-D-aspartate receptor, NMDA), and increases sensitivity to hallucinogens. In contrast, omega-3 supplementation improves cognitive function and prevents psychotic-like behavior in some animal models for schizophrenia. It also reduces oxidative stress and prevents demyelination. The historical membrane hypothesis of schizophrenia has led to explore the lipids abnormality in this disorder. This hypothesis was initially based on the observation of an abnormal membrane prostaglandin production in schizophrenia caused by a membrane arachidonic acid deficiency. It has evolved emphasizing the various PUFA membrane's roles in particular regarding oxidative stress, inflammation and regulation of the NMDA receptors. In patients with mental disorders, low omega-3 index is more frequent than in the general population. This lipid abnormality could lead to myelination abnormalities and cognitive deficits observed in patients. It could also participate in oxidative stress abnormalities and inflammation reported in schizophrenia. On the other hand, low omega-3 index deficit was reported to be associated with an increased cardiovascular risk, and omega-3 supplementation may also have a positive cardiovascular impact in psychiatric patients, even more than in the general population. The presence of membrane lipid abnormalities is also found in patients during the first psychotic episode (FEP). The omega-3 supplementation improved the recovery rate and prevented the loss of gray matter in FEP. In patients at ultra-high risk to develop a psychotic disorder (UHR), omega-3 supplementation has been associated with a reduction of the rate of conversion to psychosis and with metabolic changes, such as decreased activity of phospholipase A2. However, this study has not as yet been replicated. Not all patients exhibit lipid abnormalities. Several studies, including studies from our team, have found a bimodal distribution of lipids in patients with schizophrenia. But some studies have found differences (in PUFA) in the acute phase whereas our studies (on phospholipids) are in chronic phases. It will be interesting to study in more depth the links between these two parameters. Furthermore, we identified a subgroup which was identified with a deficit in sphingomyelin and PUFA whereas others have found an increase of sphingomyelin. Individuals with this abnormal lipid cluster had more cognitive impairments and more severe clinical symptoms. Because the niacin test is an indirect reflection of arachidonic acid levels, it has been proposed to identify a subset of patients with membrane lipids anomalies. Niacin test response is influenced by several factors related to lipid metabolism, including cannabis use and phospholipase A2 activity. Despite progress, the function and impact of membrane lipids are still poorly understood in schizophrenia. They could serve as biomarkers for identifying biological subgroups among patients with schizophrenia. In UHR patients, their predictive value on the conversion to psychosis should be tested. Omega-3 supplementation could be a promising treatment thanks to its good tolerance and acceptability. It could be more appropriate for patients with PUFA anomalies in a more personalized medical approach.
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Affiliation(s)
- A Frajerman
- Inserm U1266 - GDR 3557, institut de psychiatrie et neurosciences de Paris, Institut de Psychiatrie, Paris, France.
| | - O Kebir
- Inserm U1266 - GDR 3557, institut de psychiatrie et neurosciences de Paris, Institut de Psychiatrie, Paris, France; GHU Paris psychiatrie et neurosciences, Paris, France
| | - B Chaumette
- Inserm U1266 - GDR 3557, institut de psychiatrie et neurosciences de Paris, Institut de Psychiatrie, Paris, France; GHU Paris psychiatrie et neurosciences, Paris, France; Université Paris Descartes, Université de Paris, Paris, France
| | - C Tessier
- ERL 1157, laboratoire de spectrométrie de masse, CHU de Saint-Antoine, Paris, France
| | - A Lamazière
- Inserm UMR_S 938, département METOMICS, centre de recherche Saint-Antoine, Sorbonne Université, AP-HP, Paris, France
| | - P Nuss
- Inserm UMR_S 938, département METOMICS, centre de recherche Saint-Antoine, Sorbonne Université, AP-HP, Paris, France; Service de psychiatrie et de psychologie médicale, Hôpital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France
| | - M-O Krebs
- Inserm U1266 - GDR 3557, institut de psychiatrie et neurosciences de Paris, Institut de Psychiatrie, Paris, France; GHU Paris psychiatrie et neurosciences, Paris, France; Université Paris Descartes, Université de Paris, Paris, France
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16
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Effects of ketamine on prepubertal Wistar rats: Implications on behavioral parameters for Childhood‐Onset Schizophrenia. Int J Dev Neurosci 2019; 79:49-53. [DOI: 10.1016/j.ijdevneu.2019.10.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 10/12/2019] [Accepted: 10/14/2019] [Indexed: 02/06/2023] Open
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17
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Mellon SH, Bersani FS, Lindqvist D, Hammamieh R, Donohue D, Dean K, Jett M, Yehuda R, Flory J, Reus VI, Bierer LM, Makotkine I, Abu Amara D, Henn Haase C, Coy M, Doyle FJ, Marmar C, Wolkowitz OM. Metabolomic analysis of male combat veterans with post traumatic stress disorder. PLoS One 2019; 14:e0213839. [PMID: 30883584 PMCID: PMC6422302 DOI: 10.1371/journal.pone.0213839] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 03/02/2019] [Indexed: 12/26/2022] Open
Abstract
Posttraumatic stress disorder (PTSD) is associated with impaired major domains of psychology and behavior. Individuals with PTSD also have increased co-morbidity with several serious medical conditions, including autoimmune diseases, cardiovascular disease, and diabetes, raising the possibility that systemic pathology associated with PTSD might be identified by metabolomic analysis of blood. We sought to identify metabolites that are altered in male combat veterans with PTSD. In this case-control study, we compared metabolomic profiles from age-matched male combat trauma-exposed veterans from the Iraq and Afghanistan conflicts with PTSD (n = 52) and without PTSD (n = 51) (‘Discovery group’). An additional group of 31 PTSD-positive and 31 PTSD-negative male combat-exposed veterans was used for validation of these findings (‘Test group’). Plasma metabolite profiles were measured in all subjects using ultrahigh performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry. We identified key differences between PTSD subjects and controls in pathways related to glycolysis and fatty acid uptake and metabolism in the initial ‘Discovery group’, consistent with mitochondrial alterations or dysfunction, which were also confirmed in the ‘Test group’. Other pathways related to urea cycle and amino acid metabolism were different between PTSD subjects and controls in the ‘Discovery’ but not in the smaller ‘Test’ group. These metabolic differences were not explained by comorbid major depression, body mass index, blood glucose, hemoglobin A1c, smoking, or use of analgesics, antidepressants, statins, or anti-inflammatories. These data show replicable, wide-ranging changes in the metabolic profile of combat-exposed males with PTSD, with a suggestion of mitochondrial alterations or dysfunction, that may contribute to the behavioral and somatic phenotypes associated with this disease.
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Affiliation(s)
- Synthia H. Mellon
- Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco, CA, United States of America
- * E-mail:
| | - F. Saverio Bersani
- Department of Psychiatry and UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, United States of America
| | - Daniel Lindqvist
- Department of Psychiatry and UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, United States of America
| | - Rasha Hammamieh
- Integrative Systems Biology, US Army Medical Research and Materiel Command, USACEHR, Fort Detrick, Frederick, MD, United States of America
| | - Duncan Donohue
- Integrative Systems Biology, US Army Medical Research and Materiel Command, USACEHR, Fort Detrick, Frederick, MD, United States of America
| | - Kelsey Dean
- School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, United States of America
| | - Marti Jett
- Integrative Systems Biology, US Army Medical Research and Materiel Command, USACEHR, Fort Detrick, Frederick, MD, United States of America
| | - Rachel Yehuda
- Department of Psychiatry, James J. Peters VA Medical Center, Bronx, NY and Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Janine Flory
- Department of Psychiatry, James J. Peters VA Medical Center, Bronx, NY and Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Victor I. Reus
- Department of Psychiatry and UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, United States of America
| | - Linda M. Bierer
- Department of Psychiatry, James J. Peters VA Medical Center, Bronx, NY and Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Iouri Makotkine
- Department of Psychiatry, James J. Peters VA Medical Center, Bronx, NY and Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Duna Abu Amara
- Department of Psychiatry, New York University Langone Medical School, New York, NY, United States of America
| | - Clare Henn Haase
- Department of Psychiatry, New York University Langone Medical School, New York, NY, United States of America
| | - Michelle Coy
- Department of Psychiatry and UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, United States of America
| | - Francis J. Doyle
- School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, United States of America
| | - Charles Marmar
- Department of Psychiatry, New York University Langone Medical School, New York, NY, United States of America
- Stephen and Alexandra Cohen Veteran Center for Posttraumatic Stress and Traumatic Brain Injury, New York, NY, United States of America
| | - Owen M. Wolkowitz
- Department of Psychiatry and UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, United States of America
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18
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Dias KCF, de Almeida JC, Vasconcelos LC, Patrocínio MLV, Barbosa TM, Ximenes NC, Leitão APDA, Louchard BO, Pimenta ATÁ, Pinto FDCL, Leal LKAM, Honório Junior JER, Vasconcelos SMM. Standardized extract of Erythrina velutina Willd. attenuates schizophrenia-Like behaviours and oxidative parameters in experimental animal models. J Pharm Pharmacol 2018; 71:379-389. [PMID: 30456833 DOI: 10.1111/jphp.13039] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Accepted: 10/19/2018] [Indexed: 12/14/2022]
Abstract
OBJECTIVES To study the effects of the standardized extract from the leaves of Erythrina velutina in behavioural and oxidative parameters in the ketamine-induced schizophrenia model. METHODS Mice received ketamine (KET) or saline for 7 days. From 8th to 14th day, the animals received Erythrine (Eryt) (100, 200 or 400 mg/kg) or olanzapine (Olanz), 1 h after KET administration. At 14th day, 30 min after the last administration of KET, the open-field and pre-pulse inhibition (PPI) tests were performed. Then, the animals were sacrificed and the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) were dissected for the oxidative tests. KEY FINDINGS Ketamine increased spontaneous locomotor activity and grooming. KET decreased the PPI, which was reversed by combining it with Eryt or olanzapine. KET decreased GSH concentration in PFC and ST this was reversed by Eryt. KET increased MDA concentration in PFC and HC this was reversed by Eryt. Eryt and Olanzapine reduced MDA concentration in ST when compared to KET group. Nitrite concentration was reduced by administration of KET in the PFC. CONCLUSIONS These results demonstrate that the standardized extract of E. velutina can prevent behavioural symptoms and oxidative stress induced by repeated doses of KET.
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Affiliation(s)
- Katia Cilene Ferreira Dias
- Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Ceará, Brazil
| | - Jamily Cunha de Almeida
- Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Ceará, Brazil
| | - Luna Costa Vasconcelos
- Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Ceará, Brazil
| | | | - Talita Matias Barbosa
- Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Ceará, Brazil
| | - Naiara Coelho Ximenes
- Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Ceará, Brazil
| | | | | | | | | | | | - José Eduardo Ribeiro Honório Junior
- Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Ceará, Brazil.,School of Medicine, University Center Christus-Unichristus, Ceará, Brazil
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19
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Canever L, Freire TG, Mastella GA, Damázio L, Gomes S, Fachim I, Michels C, Carvalho G, Godói AK, Peterle BR, Gava FF, Valvassori SS, Budni J, Quevedo J, Zugno AI. Changes in behavioural parameters, oxidative stress and neurotrophins in the brain of adult offspring induced to an animal model of schizophrenia: The effects of FA deficient or FA supplemented diet during the neurodevelopmental phase. Prog Neuropsychopharmacol Biol Psychiatry 2018; 86:52-64. [PMID: 29782958 DOI: 10.1016/j.pnpbp.2018.05.014] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2017] [Revised: 05/16/2018] [Accepted: 05/17/2018] [Indexed: 01/28/2023]
Abstract
A deficiency of maternal folic acid (FA) can compromise the function and development of the brain, and may produce a susceptibility to diseases such as schizophrenia (SZ) in the later life of offspring. The aim of this study was to evaluate the effects of both FA deficient and FA supplemented diets during gestation and lactation on behavioural parameters, the markers of oxidative stress and neurotrophic factors in adult offspring which had been subjected to an animal model of SZ. Female mother rats (Dam's) were separated into experimental maternal groups, which began receiving a special diet (food) consisting of the AIN-93 diet, a control diet, or an FA deficient diet during the periods of pregnancy and lactation. Dam's receiving the control diet were further subdivided into four groups: one group received only control diet, while three groups to receive supplementation with FA at different doses (5, 10 and 50 mg/kg). Adult offspring bred from the Dam's were divided into ten groups for induction of the animal model of SZ through the administration of ketamine (Ket) (25 mg/kg). After the last administration of the drug, the animals were subjected to the behavioural tests and were then euthanized. The frontal cortex (FC) and hippocampus (Hip) were then dissected for later biochemical analysis. Our data demonstrates that Ket induced the model of SZ by altering the behavioural parameters (e.g. hyperlocomotion, social impairment, deficits in the sensory-motor profile and memory damage in the adult animals); and also caused changes in the parameters of oxidative stress (lipid hydroperoxide - LPO; 8-isoprostane - 8-ISO; 4-hydroxynonenal - 4-HNE; protein carbonyl content; superoxide dismutase - SOD and catalase - CAT) as well as in the levels of neurotrophic factors (brain-derived neurotrophic factor - BDNF and nerve growth factor - NGF) particularly within the FC of adult offspring. A deficiency in maternal FA, alone or in combination with ket, was able to induce hyperlocomotion and social impairment in the offspring with increased levels of lipid and protein damage (LPO, 8-ISO, 4-HNE, carbonylation of protein) within the FC, increased activity of antioxidant enzymes (SOD and CAT) in both of the brain structures studied, and also reduced the levels of neurotrophins (BDNF and NGF), particularly within the Hip of the adult offspring. Supplementation of FA (5, 10 and 50 mg/kg) to the Dam's was mostly able to prevent the cognitive damage which was induced by Ket in the adult animals. FA (10 and 50 mg/kg) attenuated the action of Ket in the animals in relation to the biochemical parameters, proving the possible neuroprotective effect of FA in the adulthood of offspring that were subjected to the animal model of SZ. Our study indicates that the intake of maternal FA during pregnancy and lactation plays an important role, particularly in the regulation of markers of oxidative stress and neurotrophins.
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Affiliation(s)
- L Canever
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil
| | - T G Freire
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil
| | - G A Mastella
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil
| | - L Damázio
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil
| | - S Gomes
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil
| | - I Fachim
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil
| | - C Michels
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil
| | - G Carvalho
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil
| | - A K Godói
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil
| | - B R Peterle
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil
| | - F F Gava
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil
| | - S S Valvassori
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil
| | - J Budni
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil
| | - J Quevedo
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil; Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA
| | - A I Zugno
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.
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Baéza E, Chartrin P, Bordeau T, Lessire M, Thoby JM, Gigaud V, Blanchet M, Alinier A, Leterrier C. Omega-3 polyunsaturated fatty acids provided during embryonic development improve the growth performance and welfare of Muscovy ducks (Cairina moschata). Poult Sci 2018; 96:3176-3187. [PMID: 28854755 DOI: 10.3382/ps/pex147] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Accepted: 05/10/2017] [Indexed: 12/14/2022] Open
Abstract
The welfare of ducks can be affected by unwanted behaviors such as excessive reactivity and feather pecking. Providing long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) during gestation and early life has been shown to improve the brain development and function of human and rodent offspring. The aim of this study was to test whether the pecking behavior of Muscovy ducks during rearing could be reduced by providing LC n-3 PUFA during embryonic and/or post-hatching development of ducklings. Enrichment of eggs, and consequently embryos, with LC n-3 PUFA was achieved by feeding female ducks (n-3F) a diet containing docosahexaenoic (DHA) and linolenic acids (microalgae and linseed oil). A control group of female ducks (CF) was fed a diet containing linoleic acid (soybean oil). Offspring from both groups were fed starter and grower diets enriched with DHA and linolenic acid or only linoleic acid, resulting in four treatment groups with 48 ducklings in each. Several behavioral tests were performed between 1 and 3 weeks of age to analyze the adaptation ability of ducklings. The growth performance, time budget, social interactions, feather growth, and pecking behavior of ducklings were recorded regularly during the rearing period. No significant interaction between maternal and duckling feeding was found. Ducklings from n-3F ducks had a higher body weight at day 0, 28, and 56, a lower feed conversion ratio during the growth period, and lower reactivity to stress than ducklings from CF ducks. Ducklings from n-3F ducks also exhibited a significantly reduced feather pecking frequency at 49 and 56 days of age and for the whole rearing period. Moreover, consumption of diets enriched with n-3 PUFA during the starter and grower post-hatching periods significantly improved the tibia mineralization of ducklings and the fatty acid composition of thigh muscles at 84 days of age by increasing the n-3 FA content.
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Affiliation(s)
- E Baéza
- INRA, UR83 Recherches Avicoles, F-37380 Nouzilly, France.
| | - P Chartrin
- INRA, UR83 Recherches Avicoles, F-37380 Nouzilly, France
| | - T Bordeau
- INRA, UR83 Recherches Avicoles, F-37380 Nouzilly, France
| | - M Lessire
- INRA, UR83 Recherches Avicoles, F-37380 Nouzilly, France
| | - J M Thoby
- DSM Nutritional Products France, 19 avenue Dubonnet, 92400 Courbevoie, France
| | - V Gigaud
- DSM Nutritional Products France, 19 avenue Dubonnet, 92400 Courbevoie, France
| | - M Blanchet
- Grimaud Frères Sélection, La Corbière, F-49450 Roussay, France
| | - A Alinier
- Grimaud Frères Sélection, La Corbière, F-49450 Roussay, France
| | - C Leterrier
- INRA, UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France
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Schiavone S, Trabace L. The use of antioxidant compounds in the treatment of first psychotic episode: Highlights from preclinical studies. CNS Neurosci Ther 2018. [PMID: 29542255 DOI: 10.1111/cns.12847] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Recent evidence highlighted a pathogenetic link between redox dysregulation and the early stages of psychosis. Indeed, an increasing number of studies have pointed toward an association between oxidative stress, both at central and peripheral levels, and first psychotic episode. Moreover, basal low antioxidant capacity has been shown to directly correlate with cognitive impairment in the early onset of psychosis. In this context, the possibility to use antioxidant compounds in first psychotic episode, especially as supplementation to antipsychotic therapy, has become the focus of numerous investigations on rodents with the aim to translate data on the possible effects of antioxidant therapies to large populations of patients, with a diagnosis of the first psychotic episode. In this review, we will discuss studies, published from January 1st, 2007 to July 31st, 2017, investigating the effects of antioxidant compounds on neuropathological alterations observed in different rodent models characterized by a cluster of psychotic-like symptoms reminiscent of what observed in human first psychotic episode. A final focus on the effective possibility to directly translate data obtained on rodents to humans will be also provided.
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Affiliation(s)
- Stefania Schiavone
- Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy
| | - Luigia Trabace
- Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy
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22
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Mert DG, Turgut NH, Arslanbas E, Gungor H, Kara H. The influence of quercetin on recognition memory and brain oxidative damage in a ketamine model of schizophrenia. PSYCHIAT CLIN PSYCH 2018. [DOI: 10.1080/24750573.2018.1442670] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/17/2022] Open
Affiliation(s)
- Derya Guliz Mert
- Department of Psychiatry, Cumhuriyet University Faculty of Medicine, Sivas, Turkey
| | - Nergiz Hacer Turgut
- Department of Pharmacology, Katip Çelebi University Faculty of Pharmacy, İzmir, Turkey
| | - Emre Arslanbas
- Department of Pharmacology and Toxicology, Cumhuriyet University Faculty of Veterinary Medicine, Sivas, Turkey
| | - Huseyin Gungor
- Department of Pharmacology and Toxicology, Cumhuriyet University Faculty of Veterinary Medicine, Sivas, Turkey
| | - Haki Kara
- Department of Pharmacology and Toxicology, Cumhuriyet University Faculty of Veterinary Medicine, Sivas, Turkey
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Réus GZ, Becker IRT, Scaini G, Petronilho F, Oses JP, Kaddurah-Daouk R, Ceretta LB, Zugno AI, Dal-Pizzol F, Quevedo J, Barichello T. The inhibition of the kynurenine pathway prevents behavioral disturbances and oxidative stress in the brain of adult rats subjected to an animal model of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2018; 81:55-63. [PMID: 29030243 DOI: 10.1016/j.pnpbp.2017.10.009] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2017] [Revised: 10/09/2017] [Accepted: 10/09/2017] [Indexed: 12/19/2022]
Abstract
Evidence has shown that the kynurenine pathway (KP) plays a role in the onset of oxidative stress and also in the pathophysiology of schizophrenia. The aim of this study was to use a pharmacological animal model of schizophrenia induced by ketamine to investigate if KP inhibitors could protect the brains of Wistar rats against oxidative stress and behavioral changes. Ketamine, injected at the dose of 25mg/kg, increased spontaneous locomotor activity. However, the inhibitors of tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase (IDO) and kynurenine-3-monooxygenase (KMO) were able to reverse these changes. In addition, the IDO inhibitor prevented lipid peroxidation, and decreased the levels of protein carbonyl in the prefrontal cortex (PFC), hippocampus and striatum. It also increased the activity of superoxide dismutase (SOD) in the hippocampus, as well as increasing the levels of catalase activity in the PFC and hippocampus. The TDO inhibitor prevented lipid damage in the striatum and reduced the levels of protein carbonyl in the hippocampus and striatum. Also, the TDO inhibitor increased the levels of SOD activity in the striatum and CAT activity in the hippocampus of ketamine-induced pro-oxidant effects. Lipid damage was not reversed by the KMO inhibitor. The KMO inhibitor increased the levels of SOD activity in the hippocampus, and reduced the levels of protein carbonyl while elevating the levels of CAT activity in the striatum of rats that had been injected with ketamine. Our findings revealed that the KP pathway could be a potential mechanism by which a schizophrenia animal model induced by ketamine could cause interference by producing behavioral disturbance and inducing oxidative stress in the brain, suggesting that the inhibition of the KP pathway could be a potential target in treating schizophrenia.
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Affiliation(s)
- Gislaine Z Réus
- Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
| | - Indianara R T Becker
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
| | - Giselli Scaini
- Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA; Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA
| | - Fabricia Petronilho
- Laboratory of Clinical and Experimental Pathophysiology, Postgraduate Program in Health Sciences, University of Southern Santa Catarina (UNISUL), Tubarão, SC, Brazil
| | - Jean P Oses
- Translational Science on Brain Disorders, Department of Health and Behavior, Catholic University of Pelotas, Pelotas, RS, Brazil
| | - Rima Kaddurah-Daouk
- Department of Psychiatry and Behavioral Sciences, Duke Institute for Brain Sciences, Duke University, Durham, NC, USA; Programa de Pós-graduação em Saúde Coletiva, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
| | - Luciane B Ceretta
- Neuroscience Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA
| | - Alexandra I Zugno
- Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
| | - Felipe Dal-Pizzol
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
| | - João Quevedo
- Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil; Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil; Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA; Neuroscience Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA
| | - Tatiana Barichello
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil; Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA; Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
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Yadav M, Parle M, Jindal DK, Sharma N. Potential effect of spermidine on GABA, dopamine, acetylcholinesterase, oxidative stress and proinflammatory cytokines to diminish ketamine-induced psychotic symptoms in rats. Biomed Pharmacother 2018; 98:207-213. [DOI: 10.1016/j.biopha.2017.12.016] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2017] [Revised: 11/13/2017] [Accepted: 12/04/2017] [Indexed: 12/31/2022] Open
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Yadav M, Parle M, Jindal DK, Dhingra S. Protective effects of stigmasterol against ketamine-induced psychotic symptoms: Possible behavioral, biochemical and histopathological changes in mice. Pharmacol Rep 2018; 70:591-599. [PMID: 29679883 DOI: 10.1016/j.pharep.2018.01.001] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Revised: 11/30/2017] [Accepted: 01/09/2018] [Indexed: 01/18/2023]
Abstract
BACKGROUND Stigmasterol, a naturally occurring phytoestrogen has been reported to possess many pharmacological activities. The aim of the present study was to screen the effect of stigmasterol against ketamine-induced mice model of psychosis. METHODS The behavioural studies included an assessment of locomotor activity, stereotypic behaviours, immobility duration, step down latency and effects on catalepsy. Biochemical estimations involved the estimations of GABA, dopamine, GSH, MDA, TNF-α, total protein content and AChE activity. Histopathological changes and effect on androgenic parameters were also evaluated. RESULTS Stigmasterol treated animals showed significant decrease in locomotor activity, stereotypic behaviours, immobility duration and increased step down latency. Biochemical estimations revealed increased GABA, GSH levels and decreased dopamine, MDA, TNF-α levels and AChE activity. These findings were confirmed by histopathological changes in the cortex part of the brain. Further, stigmasterol was not found to cause catalepsy and any adverse effect on the reproductive system. CONCLUSION This study concluded that stigmasterol could ameliorate ketamine-induced behavioral, biochemical and histopathological alterations in mice showing its potential effects in the management of psychotic symptoms.
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Affiliation(s)
- Monu Yadav
- Faculty of Medical Sciences, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, India
| | - Milind Parle
- Faculty of Medical Sciences, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, India.
| | - Deepak Kumar Jindal
- Faculty of Medical Sciences, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, India
| | - Sameer Dhingra
- Faculty of Medical Sciences, School of Pharmacy, The University of the West Indies, St. Augustine, Trinidad and Tobago
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Healy-Stoffel M, Levant B. N-3 (Omega-3) Fatty Acids: Effects on Brain Dopamine Systems and Potential Role in the Etiology and Treatment of Neuropsychiatric Disorders. CNS & NEUROLOGICAL DISORDERS DRUG TARGETS 2018; 17:216-232. [PMID: 29651972 PMCID: PMC6563911 DOI: 10.2174/1871527317666180412153612] [Citation(s) in RCA: 82] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/18/2017] [Revised: 11/01/2017] [Accepted: 02/08/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & OBJECTIVE A number of neuropsychiatric disorders, including Parkinson's disease, schizophrenia, attention deficit hyperactivity disorder, and, to some extent, depression, involve dysregulation of the brain dopamine systems. The etiology of these diseases is multifactorial, involving genetic and environmental factors. Evidence suggests that inadequate levels of n-3 (omega- 3) polyunsaturated fatty acids (PUFA) in the brain may represent a risk factor for these disorders. These fatty acids, which are derived from the diet, are a major component of neuronal membranes and are of particular importance in brain development and function. Low levels of n-3 PUFAs in the brain affect the brain dopamine systems and, when combined with appropriate genetic and other factors, increase the risk of developing these disorders and/or the severity of the disease. This article reviews the neurobiology of n-3 PUFAs and their effects on dopaminergic function. CONCLUSION Clinical studies supporting their role in the etiologies of diseases involving the brain dopamine systems and the potential of n-3 PUFAs in the treatment of these disorders are discussed.
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Affiliation(s)
| | - Beth Levant
- Department of Pharmacology, Toxicology, and Therapeutics and the Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS, USA
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Yadav M, Parle M, Sharma N, Dhingra S, Raina N, Jindal DK. Brain targeted oral delivery of doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles against ketamine induced psychosis: behavioral, biochemical, neurochemical and histological alterations in mice. Drug Deliv 2017; 24:1429-1440. [PMID: 28942680 PMCID: PMC8241001 DOI: 10.1080/10717544.2017.1377315] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 09/01/2017] [Accepted: 09/05/2017] [Indexed: 12/28/2022] Open
Abstract
To develop statistically optimized brain targeted Tween 80 coated chitosan nanoparticulate formulation for oral delivery of doxycycline hydrochloride for the treatment of psychosis and to evaluate its protective effect on ketamine induced behavioral, biochemical, neurochemical and histological alterations in mice. 32 full factorial design was used to optimize the nanoparticulate formulation to minimize particle size and maximize entrapment efficiency, while independent variables chosen were concentration of chitosan and Tween 80. The optimized formulation was characterized by particle size, drug entrapment efficiency, Fourier transform infrared, Transmission electron microscopy analysis and drug release behavior. Pure doxycycline hydrochloride (25 and 50 mg/kg, p.o.) and optimized doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles (DCNPopt) (equivalent to 25 mg/kg doxycycline hydrochloride, p.o.) were explored against ketamine induced psychosis in mice. The experimental studies for DCNPopt, with mean particle size 237 nm and entrapment efficiency 78.16%, elucidated that the formulation successfully passed through blood brain barrier and exhibited significant antipsychotic activity. The underlying mechanism of action was further confirmed by behavioral, biochemical, neurochemical estimations and histopathological study. Significantly enhanced GABA and GSH level and diminished MDA, TNF-α and dopamine levels were observed after administration of DCNPopt at just half the dose of pure doxycycline hydrochloride, showing better penetration of doxycyline hydrochloride in the form of Tween 80 coated nanoparticles through blood brain barrier. This study demonstrates the hydrophilic drug doxycycline hydrochloride, loaded in Tween 80 coated chitosan nanoparticles, can be effectively brain targeted through oral delivery and therefore represents a suitable approach for the treatment of psychotic symptoms.
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Affiliation(s)
- Monu Yadav
- Faculty of Medical Sciences, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science & Technology, Hisar, India
| | - Milind Parle
- Faculty of Medical Sciences, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science & Technology, Hisar, India
| | - Nidhi Sharma
- Faculty of Medical Sciences, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science & Technology, Hisar, India
| | - Sameer Dhingra
- Faculty of Medical Sciences, School of Pharmacy, The University of the West Indies, St. Augustine, Trinidad and Tobago
| | - Neha Raina
- Faculty of Medical Sciences, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science & Technology, Hisar, India
| | - Deepak Kumar Jindal
- Faculty of Medical Sciences, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science & Technology, Hisar, India
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Tian L, Hui CW, Bisht K, Tan Y, Sharma K, Chen S, Zhang X, Tremblay ME. Microglia under psychosocial stressors along the aging trajectory: Consequences on neuronal circuits, behavior, and brain diseases. Prog Neuropsychopharmacol Biol Psychiatry 2017; 79:27-39. [PMID: 28095309 DOI: 10.1016/j.pnpbp.2017.01.007] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2016] [Revised: 12/30/2016] [Accepted: 01/13/2017] [Indexed: 12/18/2022]
Abstract
Mounting evidence indicates the importance of microglia for proper brain development and function, as well as in complex stress-related neuropsychiatric disorders and cognitive decline along the aging trajectory. Considering that microglia are resident immune cells of the brain, a homeostatic maintenance of their effector functions that impact neuronal circuitry, such as phagocytosis and secretion of inflammatory factors, is critical to prevent the onset and progression of these pathological conditions. However, the molecular mechanisms by which microglial functions can be properly regulated under healthy and pathological conditions are still largely unknown. We aim to summarize recent progress regarding the effects of psychosocial stress and oxidative stress on microglial phenotypes, leading to neuroinflammation and impaired microglia-synapse interactions, notably through our own studies of inbred mouse strains, and most importantly, to discuss about promising therapeutic strategies that take advantage of microglial functions to tackle such brain disorders in the context of adult psychosocial stress or aging-induced oxidative stress.
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Affiliation(s)
- Li Tian
- Neuroscience Center, University of Helsinki, Viikinkaari 4, Helsinki FIN-00014, Finland; Psychiatry Research Center, Beijing Huilongguan Hospital, Peking University, Beijing, China.
| | - Chin Wai Hui
- Axe Neurosciences, Centre de recherche du CHU de Québec, Québec, Canada
| | - Kanchan Bisht
- Axe Neurosciences, Centre de recherche du CHU de Québec, Québec, Canada
| | - Yunlong Tan
- Psychiatry Research Center, Beijing Huilongguan Hospital, Peking University, Beijing, China
| | - Kaushik Sharma
- Axe Neurosciences, Centre de recherche du CHU de Québec, Québec, Canada
| | - Song Chen
- Psychiatry Research Center, Beijing Huilongguan Hospital, Peking University, Beijing, China; Beijing Key Laboratory of Mental Disorders and Center of Schizophrenia, Beijing Institute for Brain Disorders, Beijing Anding Hospital, Capital Medical University, China
| | - Xiangyang Zhang
- Psychiatry Research Center, Beijing Huilongguan Hospital, Peking University, Beijing, China; Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Marie-Eve Tremblay
- Axe Neurosciences, Centre de recherche du CHU de Québec, Québec, Canada.
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Mitra S, Natarajan R, Ziedonis D, Fan X. Antioxidant and anti-inflammatory nutrient status, supplementation, and mechanisms in patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2017; 78:1-11. [PMID: 28499901 DOI: 10.1016/j.pnpbp.2017.05.005] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Revised: 05/06/2017] [Accepted: 05/08/2017] [Indexed: 10/19/2022]
Abstract
Over 50 million people around the world suffer from schizophrenia, a severe mental illness characterized by misinterpretation of reality. Although the exact causes of schizophrenia are still unknown, studies have indicated that inflammation and oxidative stress may play an important role in the etiology of the disease. Pro-inflammatory cytokines are crucial for normal central nervous development and proper functioning of neural networks and neurotransmitters. Patients with schizophrenia tend to have abnormal immune activation resulting in elevated pro-inflammatory cytokine levels, ultimately leading to functional brain impairments. Patients with schizophrenia have also been found to suffer from oxidative stress, a result of an imbalance between the production of free radicals and the ability to detoxify their harmful effects. Furthermore, inflammation and oxidative stress are implicated to be related to the severity of psychotic symptoms. Several nutrients are known to have anti-inflammatory and antioxidant functions through various mechanisms in our body. The present review evaluates studies and literature that address the status and supplementation of omega-3 polyunsaturated fatty acids, vitamin D, B vitamins (B6, folate, B12), vitamin E, and carotenoids in different stages of schizophrenia. The possible anti-inflammatory and antioxidant mechanisms of action of each nutrient are discussed.
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Affiliation(s)
- Sumedha Mitra
- Department of Psychiatry, UMass Memorial Medical Center/University of Massachusetts Medical School, One Biotech, 365 Plantation Street, Worcester, MA 01605, USA
| | - Radhika Natarajan
- Department of Psychiatry, UMass Memorial Medical Center/University of Massachusetts Medical School, One Biotech, 365 Plantation Street, Worcester, MA 01605, USA
| | - Douglas Ziedonis
- Department of Psychiatry, UMass Memorial Medical Center/University of Massachusetts Medical School, One Biotech, 365 Plantation Street, Worcester, MA 01605, USA
| | - Xiaoduo Fan
- Department of Psychiatry, UMass Memorial Medical Center/University of Massachusetts Medical School, One Biotech, 365 Plantation Street, Worcester, MA 01605, USA.
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30
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Yang X, Sun L, Zhao A, Hu X, Qing Y, Jiang J, Yang C, Xu T, Wang P, Liu J, Zhang J, He L, Jia W, Wan C. Serum fatty acid patterns in patients with schizophrenia: a targeted metabonomics study. Transl Psychiatry 2017; 7:e1176. [PMID: 28742081 PMCID: PMC5538128 DOI: 10.1038/tp.2017.152] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Revised: 04/25/2017] [Accepted: 06/07/2017] [Indexed: 12/21/2022] Open
Abstract
Previous studies have indicated that schizophrenia is linked to abnormal lipid metabolism. Free fatty acids (FFAs) in peripheral blood can reflect the status of lipid metabolism in human body. The purpose of this study was to scan the FFA pattern and elucidate the characteristics of lipid metabolic abnormality in schizophrenia patients. One hundred and ten patients with schizophrenia (SCZs) and 109 healthy controls (HCs) were included in the study and divided into a discovery set and a validation set. Forty-seven serum FFAs were detected by UPLC-QTOF-MS and 39 of them were absolutely quantified by establishing standard curves. Monounsaturated fatty acids (MUFAs) and ω-6 polyunsaturated fatty acids (ω-6 PUFAs) were significantly increased in SCZs compared with HCs. Desaturation from saturated fatty acids to MUFAs and β-oxidation were enhanced, as estimated by the ratios of products to precursors. These results suggest that lipolysis and β-oxidation are upregulated in SCZ, presumably resulting from insufficient brain energy supply.
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Affiliation(s)
- X Yang
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Key Laboratory of Translational Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University, Shanghai, China
| | - L Sun
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Key Laboratory of Translational Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University, Shanghai, China
| | - A Zhao
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - X Hu
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Key Laboratory of Translational Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University, Shanghai, China
| | - Y Qing
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Key Laboratory of Translational Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University, Shanghai, China
| | - J Jiang
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Key Laboratory of Translational Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University, Shanghai, China
| | - C Yang
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Key Laboratory of Translational Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University, Shanghai, China
| | - T Xu
- Discipline of Neuroscience, Department of Anatomy, Histology and Embryology, Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - P Wang
- The Fourth People’s Hospital of Wuhu, Wuhu, China
| | - J Liu
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - J Zhang
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Key Laboratory of Translational Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University, Shanghai, China
| | - L He
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Key Laboratory of Translational Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University, Shanghai, China
| | - W Jia
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - C Wan
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Key Laboratory of Translational Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University, Shanghai, China
- Collaborative Innovation Center of Genetics and Development, Shanghai, China
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31
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Yadav M, Jindal DK, Dhingra MS, Kumar A, Parle M, Dhingra S. Protective effect of gallic acid in experimental model of ketamine-induced psychosis: possible behaviour, biochemical, neurochemical and cellular alterations. Inflammopharmacology 2017; 26:413-424. [PMID: 28577133 DOI: 10.1007/s10787-017-0366-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Accepted: 05/26/2017] [Indexed: 12/17/2022]
Abstract
Gallic acid has been reported to possess a number of psychopharmacological activities. These activities are attributed to the antioxidant potential due to the presence of phenolic moeity. The present study was carried out to investigate the protective effects of gallic acid in an experimental model of ketamine-induced psychosis in mice. Ketamine (50 mg/kg, i.p.) was used to induce stereotyped psychotic behavioural symptoms in mice. Behavioural studies (locomotor activity, stereotype behaviour, immobility duration and memory retention) were carried out to investigate the protective of gallic acid on ketamine-induced psychotic symptoms, followed by biochemical and neurochemical changes and cellular alterations in the brain. Chronic treatment with gallic acid for 15 consecutive days significantly attenuated stereotyped behavioural symptoms in mice. Biochemical estimations revealed that gallic acid reduced the lipid peroxidation and restored the total brain proteins. Furthermore, gallic acid remarkably reduced the dopamine levels, AChE activity and inflammatory surge (serum TNF-α), and increased the levels of GABA and increased glutathione in mice. The study revealed that gallic acid could ameliorate psychotic symptoms and biochemical changes in mice, indicating protective effects in psychosis.
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Affiliation(s)
- Monu Yadav
- Department of Pharmaceutical Sciences, Faculty of Medical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, 125001, India
| | - Deepak Kumar Jindal
- Department of Pharmaceutical Sciences, Faculty of Medical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, 125001, India
| | - Mamta Sachdeva Dhingra
- University Institute of Pharmaceutical Sciences, UGC Center of Advanced Study (UGC-CAS) in Pharmaceutical Sciences, Panjab University, Chandigarh, India
| | - Anil Kumar
- University Institute of Pharmaceutical Sciences, UGC Center of Advanced Study (UGC-CAS) in Pharmaceutical Sciences, Panjab University, Chandigarh, India
| | - Milind Parle
- Department of Pharmaceutical Sciences, Faculty of Medical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, 125001, India
| | - Sameer Dhingra
- Faculty of Medical Sciences, School of Pharmacy, The University of the West Indies, St. Augustine, Trinidad and Tobago.
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Ketamine potentiates oxidative stress and influences behavior and inflammation in response to lipolysaccharide (LPS) exposure in early life. Neuroscience 2017; 353:17-25. [DOI: 10.1016/j.neuroscience.2017.04.016] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Revised: 04/10/2017] [Accepted: 04/12/2017] [Indexed: 02/07/2023]
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Heylmann ASA, Canever L, Gress K, Gomes ST, Fachim I, Michels C, Stopassoli GC, Mastella GA, Steckert AV, Damiani AP, de Andrade VM, Quevedo J, Zugno AI. Pre-clinical investigation of Diabetes Mellitus as a risk factor for schizophrenia. Behav Brain Res 2017; 326:154-164. [PMID: 28286284 DOI: 10.1016/j.bbr.2017.02.043] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Revised: 02/21/2017] [Accepted: 02/24/2017] [Indexed: 10/20/2022]
Abstract
This study investigated the behavioral and biochemical parameters of DM1 as a risk factor in an animal model of schizophrenia (SZ). All groups: 1 Control (saline+saline); 2 Alloxan (alloxan+saline); 3 Ketamine (saline+ketamine); 4 (Alloxan+Ketamine) were fasted for a period of 18h before the subsequent induction of DM via a single intraperitoneal (i.p) injection of alloxan (150mg/kg). From the 4th to the 10th days, the animals were injected i.p with ketamine (25mg/kg) or saline, once a day, to induce a model of SZ and 30min after the last administration were subjected to behavioral testing. After, the animals were decapitated and the brain structures were removed. Ketamine induced hyperactivity and in the social interaction, ketamine, alloxan and the association of alloxan+ketamine increased the latency and decreased the number of contacts between animals. The animals from the ketamine, alloxan and alloxan+ketamine groups showed a prepulse startle reflex (PPI) deficit at the three intensities (65, 70 and 75dB). Ketamine was shown to be capable of increasing the activity of acetylcholinesterase (AChE) in the brain structures. Combination of alloxan+ketamine seems to have an exacerbated effect within the cholinergic system. For lipid peroxidation and protein carbonyls, alloxan+ketamine appear to have intensified lipid and protein damage in the three structures. Ketamine and the combination of ketamine+alloxan induced DNA damage in both frequency and damage index. This research found a relationship between DM1 and SZ.
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Affiliation(s)
- Alexandra S Almeida Heylmann
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil
| | - Lara Canever
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil
| | - Katia Gress
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil
| | - Sarah T Gomes
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil
| | - Isadora Fachim
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil
| | - Carolina Michels
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil
| | - Geórgia C Stopassoli
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil
| | - Gustavo A Mastella
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil
| | - Amanda V Steckert
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil
| | - Adriani P Damiani
- Laboratório de Biologia Celular e Molecular, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
| | - Vanessa M de Andrade
- Laboratório de Biologia Celular e Molecular, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
| | - João Quevedo
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil; Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, Medical School, University of Texas Health Science Center at Houston, Houston, TX 77054, USA
| | - Alexandra I Zugno
- Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil.
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34
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Lipids in psychiatric disorders and preventive medicine. Neurosci Biobehav Rev 2017; 76:336-362. [DOI: 10.1016/j.neubiorev.2016.06.002] [Citation(s) in RCA: 115] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Revised: 05/06/2016] [Accepted: 06/06/2016] [Indexed: 01/12/2023]
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Macêdo PFCD, de Melo JSV, Costa LAR, Braz GRF, de Sousa SM, Lagranha CJ, Hornsby MBDO. Fish oil and treadmill exercise have age-dependent effects on episodic memory and oxidative state of the hippocampus. Appl Physiol Nutr Metab 2017; 42:503-510. [DOI: 10.1139/apnm-2016-0454] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
There is a growing interest to better understand how lifestyle choices can improve memory functions. Treadmill exercise and long-chain n-3 polyunsaturated fatty acids found in fish oil are able to stimulate hippocampal antioxidant defenses and improve memory. The aim was to test whether fish oil and exercise can improve rat’s performance on memory tasks and optimize hippocampal antioxidant state in an age-dependent manner. Therefore, young and adult rats were exercised and received fish oil during 4 weeks. The exercise was performed for 30 min/day, with the speed gradually increasing from the first to the last week. Afterwards, episodic memory was measured by the recognition of object identity and spatial location. Hippocampal oxidative state was investigated with the levels of malondialdehyde (MDA), carbonyls content, antioxidant enzymatic activity (superoxide dismutase (SOD), catalase (CAT)), and antioxidant nonenzymatic activity (reduced glutathione, sulfhydryl content). The adult rats treated with fish oil and exercise (FO&EX) were able to recognize object’s shape and placement; however, FO&EX young rats had impaired spatial recognition (p < 0.05). The FO&EX young rats did not have reduced MDA or carbonyl content, though either fish oil or exercise reduced MDA (p < 0.05) and carbonyl levels (p < 0.01). Exercise increased SOD (p < 0.001) and CAT activities (p < 0.05), and fish oil enhanced SOD activity (p < 0.05) in young rats. At adulthood, exercise increased MDA levels (p < 0.05), and FO&EX reduced MDA (p < 0.001). Finally, exercise and fish oil improved nonenzymatic antioxidant defense (p < 0.05) only in adult rats. Results support age-dependent effects of fish oil and exercise on memory and oxidative state of the hippocampus during either neurodevelopment or adulthood.
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Affiliation(s)
| | | | - Laís Alves Ribeiro Costa
- Department of Nutrition/Health Sciences Center, Federal University of Pernambuco, Campus of Recife, Recife – PE 50670-901, Brazil
| | - Glauber Rudá F. Braz
- Laboratory of Biochemistry and Exercise Biochemistry, Federal University of Pernambuco, Campus of Vitoria de Santo Antao, Vitoria de Santo Antao – PE 55608-680, Brazil
| | - Shirley M. de Sousa
- Laboratory of Biochemistry and Exercise Biochemistry, Federal University of Pernambuco, Campus of Vitoria de Santo Antao, Vitoria de Santo Antao – PE 55608-680, Brazil
| | - Cláudia J. Lagranha
- Laboratory of Biochemistry and Exercise Biochemistry, Federal University of Pernambuco, Campus of Vitoria de Santo Antao, Vitoria de Santo Antao – PE 55608-680, Brazil
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Fortunato JJ, da Rosa N, Martins Laurentino AO, Goulart M, Michalak C, Borges LP, da Cruz Cittadin Soares E, Reis PA, de Castro Faria Neto HC, Petronilho F. Effects of ω-3 fatty acids on stereotypical behavior and social interactions in Wistar rats prenatally exposed to lipopolysaccarides. Nutrition 2017; 35:119-127. [DOI: 10.1016/j.nut.2016.10.019] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Revised: 10/21/2016] [Accepted: 10/29/2016] [Indexed: 02/07/2023]
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Xiao W, Ye F, Ma L, Tang X, Li J, Dong H, Sha W, Zhang X. Atypical antipsychotic treatment increases glial cell line-derived neurotrophic factor serum levels in drug-free schizophrenic patients along with improvement of psychotic symptoms and therapeutic effects. Psychiatry Res 2016; 246:617-622. [PMID: 27836239 DOI: 10.1016/j.psychres.2016.11.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Revised: 10/26/2016] [Accepted: 11/02/2016] [Indexed: 01/16/2023]
Abstract
Glial cell line-derived neurotrophic factor (GDNF) plays an increasingly vital role in the pathogenesis of neuropsychiatric illnesses. Antipsychotic medications were shown to stimulate GDNF secretion from C6 glioma cells. The aims of this study were to investigate the serum concentration of GDNF, to monitor the therapeutic effect of atypical antipsychotics related to GDNF levels in drug-free schizophrenia patients, and to examine these levels in relation to psychotic symptoms. We recruited 138 drug-free schizophrenic patients and compared them with 77 matched healthy subjects. All patients were treated with atypical antipsychotic monotherapy. GDNF serum levels and psychiatric symptoms were assessed at baseline and after 2, 4, 6 and 8 weeks. GDNF levels gradually increased accompanied by a reduction in psychiatric symptoms during antipsychotic therapy. The levels of GDNF in responders were significantly increased after 8 weeks of treatment, however, no significant change was found in non-responders. Furthermore, a negative association between GDNF levels following pharmacotherapy and disease duration in schizophrenic subjects could be observed. The present study suggests that GDNF may be involved in the etiology of schizophrenia and pharmacological treatment.
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Affiliation(s)
- Wenhuan Xiao
- Department of Psychiatry, Affiliated WuTaiShan Hospital of Medical College of Yangzhou University, Yangzhou 225003, PR China
| | - Fei Ye
- Department of Psychiatry, Affiliated WuTaiShan Hospital of Medical College of Yangzhou University, Yangzhou 225003, PR China
| | - Li Ma
- Department of Psychiatry, Affiliated WuTaiShan Hospital of Medical College of Yangzhou University, Yangzhou 225003, PR China
| | - Xiaowei Tang
- Department of Psychiatry, Affiliated WuTaiShan Hospital of Medical College of Yangzhou University, Yangzhou 225003, PR China
| | - Jin Li
- Department of Psychiatry, Affiliated WuTaiShan Hospital of Medical College of Yangzhou University, Yangzhou 225003, PR China
| | - Hui Dong
- Department of Psychiatry, Affiliated WuTaiShan Hospital of Medical College of Yangzhou University, Yangzhou 225003, PR China
| | - Weiwei Sha
- Department of Psychiatry, Affiliated WuTaiShan Hospital of Medical College of Yangzhou University, Yangzhou 225003, PR China
| | - Xiaobin Zhang
- Department of Psychiatry, Affiliated WuTaiShan Hospital of Medical College of Yangzhou University, Yangzhou 225003, PR China.
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Ermilova I, Lyubartsev AP. Extension of the Slipids Force Field to Polyunsaturated Lipids. J Phys Chem B 2016; 120:12826-12842. [DOI: 10.1021/acs.jpcb.6b05422] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- Inna Ermilova
- Department of Materials and
Environmental Chemistry, Stockholm University, SE 106 91 Stockholm, Sweden
| | - Alexander P. Lyubartsev
- Department of Materials and
Environmental Chemistry, Stockholm University, SE 106 91 Stockholm, Sweden
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Abstract
Abstract
Ω-3 unsaturated fatty acids are compounds belonging to the group of essential fatty acids (EFAs). The history of the discovery of EFAs dates back to the 1930s of the twentieth century, however, growing interest in ω-3 EFAs in the context of mental health has been observed since the year 2000. In view of their multidirectional action, these compounds are a promising form of adjunctive therapy of many illnesses, including psychiatric disorders. The present article aims to review the literature on the clinical applicability of ω-3 EFAs in treating schizophrenia. We present the results of preclinical studies in this area and the mechanisms of ω-3 EFAs action discussed by the authors. The randomized controlled trials (RCTs) evaluating the possibility of using ω-3 EFAs in schizophrenia are characterized in detail. The results of the tests are not clear, which may result from the methodological diversity of interventions made. Ω-3 EFAs seem to be a promising form of adjunctive therapy of schizophrenia. Further research is needed, which will allow for defining groups of patients in which intervention will bring the expected results.
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Knöchel C, Voss M, Grüter F, Alves GS, Matura S, Sepanski B, Stäblein M, Wenzler S, Prvulovic D, Carvalho AF, Oertel-Knöchel V. Omega 3 Fatty Acids: Novel Neurotherapeutic Targets for Cognitive Dysfunction in Mood Disorders and Schizophrenia? Curr Neuropharmacol 2016; 13:663-80. [PMID: 26467414 PMCID: PMC4761636 DOI: 10.2174/1570159x13666150630173047] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2015] [Revised: 02/25/2015] [Accepted: 02/27/2015] [Indexed: 01/23/2023] Open
Abstract
An increasing body of evidences from preclinical as well as epidemiological and clinical
studies suggest a potential beneficial role of dietary intake of omega-3 fatty acids for cognitive functioning.
In this narrative review, we will summarize and discuss recent findings from epidemiological, interventional
and experimental studies linking dietary consumption of omega-3 fatty acids to cognitive
function in healthy adults. Furthermore, affective disorders and schizophrenia (SZ) are characterized
by cognitive dysfunction encompassing several domains. Cognitive dysfunction is closely related to impaired functioning
and quality of life across these conditions. Therefore, the current review focues on the potential influence of omega-3 fatty
acids on cognition in SZ and affective disorders. In sum, current data predominantly from mechanistic models and animal
studies suggest that adjunctive omega-3 fatty acid supplementation could lead to improved cognitive functioning in SZ
and affective disorders. However, besides its translational promise, evidence for clinical benefits in humans has been
mixed. Notwithstanding evidences indicate that adjunctive omega-3 fatty acids may have benefit for affective symptoms
in both unipolar and bipolar depression, to date no randomized controlled trial had evaluated omega-3 as cognitive
enhancer for mood disorders, while a single published controlled trial suggested no therapeutic benefit for cognitive
improvement in SZ. Considering the pleiotropic mechanisms of action of omega-3 fatty acids, the design of well-designed
controlled trials of omega-3 supplementation as a novel, domain-specific, target for cognitive impairment in SZ and
affective disorders is warranted.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Viola Oertel-Knöchel
- Laboratory for Neuroimaging, Dept. of Psychiatry, Dept. of Psychiatry, Psychosomatic Medicine and Psychotherapy; Heinrich-Hoffmann-Str. 10, Goethe-University, 60528 Frankfurt
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Kitson AP, Metherel AH, Chen CT, Domenichiello AF, Trépanier MO, Berger A, Bazinet RP. Effect of dietary docosahexaenoic acid (DHA) in phospholipids or triglycerides on brain DHA uptake and accretion. J Nutr Biochem 2016; 33:91-102. [PMID: 27135386 DOI: 10.1016/j.jnutbio.2016.02.009] [Citation(s) in RCA: 75] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Revised: 01/27/2016] [Accepted: 02/11/2016] [Indexed: 11/28/2022]
Abstract
Tracer studies suggest that phospholipid DHA (PL-DHA) more effectively targets the brain than triglyceride DHA (TAG-DHA), although the mechanism and whether this translates into higher brain DHA concentrations are not clear. Rats were gavaged with [U-(3)H]PL-DHA and [U-(3)H]TAG-DHA and blood sampled over 6h prior to collection of brain regions and other tissues. In another experiment, rats were supplemented for 4weeks with TAG-DHA (fish oil), PL-DHA (roe PL) or a mixture of both for comparison to a low-omega-3 diet. Brain regions and other tissues were collected, and blood was sampled weekly. DHA accretion rates were estimated using the balance method. [U-(3)H]PL-DHA rats had higher radioactivity in cerebellum, hippocampus and remainder of brain, with no differences in other tissues despite higher serum lipid radioactivity in [U-(3)H]TAG-DHA rats. TAG-DHA, PL-DHA or a mixture were equally effective at increasing brain DHA. There were no differences between DHA-supplemented groups in brain region, whole-body, or tissue DHA accretion rates except heart and serum TAG where the PL-DHA/TAG-DHA blend was higher than TAG-DHA. Apparent DHA β-oxidation was not different between DHA-supplemented groups. This indicates that more labeled DHA enters the brain when consumed as PL; however, this may not translate into higher brain DHA concentrations.
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Affiliation(s)
- Alex P Kitson
- Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, M5S3E2, Canada
| | - Adam H Metherel
- Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, M5S3E2, Canada
| | - Chuck T Chen
- Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, M5S3E2, Canada
| | | | - Marc-Olivier Trépanier
- Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, M5S3E2, Canada
| | - Alvin Berger
- Arctic Nutrition AS, NO-6155, Ørsta, Norway; Department of Food Science & Nutrition, University of Minnesota, St. Paul, MN, 55108-1038, USA
| | - Richard P Bazinet
- Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, M5S3E2, Canada.
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Abstract
Despite a lack of recent progress in the treatment of schizophrenia, our understanding of its genetic and environmental causes has considerably improved, and their relationship to aberrant patterns of neurodevelopment has become clearer. This raises the possibility that 'disease-modifying' strategies could alter the course to - and of - this debilitating disorder, rather than simply alleviating symptoms. A promising window for course-altering intervention is around the time of the first episode of psychosis, especially in young people at risk of transition to schizophrenia. Indeed, studies performed in both individuals at risk of developing schizophrenia and rodent models for schizophrenia suggest that pre-diagnostic pharmacotherapy and psychosocial or cognitive-behavioural interventions can delay or moderate the emergence of psychosis. Of particular interest are 'hybrid' strategies that both relieve presenting symptoms and reduce the risk of transition to schizophrenia or another psychiatric disorder. This Review aims to provide a broad-based consideration of the challenges and opportunities inherent in efforts to alter the course of schizophrenia.
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Lindberg D, Shan D, Ayers-Ringler J, Oliveros A, Benitez J, Prieto M, McCullumsmith R, Choi DS. Purinergic signaling and energy homeostasis in psychiatric disorders. Curr Mol Med 2016; 15:275-95. [PMID: 25950756 DOI: 10.2174/1566524015666150330163724] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2014] [Revised: 02/22/2015] [Accepted: 03/24/2015] [Indexed: 12/11/2022]
Abstract
Purinergic signaling regulates numerous vital biological processes in the central nervous system (CNS). The two principle purines, ATP and adenosine act as excitatory and inhibitory neurotransmitters, respectively. Compared to other classical neurotransmitters, the role of purinergic signaling in psychiatric disorders is not well understood or appreciated. Because ATP exerts its main effect on energy homeostasis, neuronal function of ATP has been underestimated. Similarly, adenosine is primarily appreciated as a precursor of nucleotide synthesis during active cell growth and division. However, recent findings suggest that purinergic signaling may explain how neuronal activity is associated neuronal energy charge and energy homeostasis, especially in mental disorders. In this review, we provide an overview of the synaptic function of mitochondria and purines in neuromodulation, synaptic plasticity, and neuron-glia interactions. We summarize how mitochondrial and purinergic dysfunction contribute to mental illnesses such as schizophrenia, bipolar disorder, autism spectrum disorder (ASD), depression, and addiction. Finally, we discuss future implications regarding the pharmacological targeting of mitochondrial and purinergic function for the treatment of psychiatric disorders.
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Affiliation(s)
| | | | | | | | | | | | | | - D-S Choi
- Neurobiology of Disease Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
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Réus GZ, Abaleira HM, Titus SE, Arent CO, Michels M, da Luz JR, dos Santos MAB, Carlessi AS, Matias BI, Bruchchen L, Steckert AV, Ceretta LB, Dal-Pizzol F, Quevedo J. Effects of ketamine administration on the phosphorylation levels of CREB and TrKB and on oxidative damage after infusion of MEK inhibitor. Pharmacol Rep 2016; 68:177-84. [DOI: 10.1016/j.pharep.2015.08.010] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2015] [Revised: 07/31/2015] [Accepted: 08/13/2015] [Indexed: 12/20/2022]
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Abstract
BACKGROUND In humans, omega-3 fatty acids are necessary for cell membranes, brain function and nerve transmission continuation. When animals are exposed to a new environment-or as a result of an apomorphine application that creates an agonistic effect on D1 and D2 receptors-they display behavioral reactions like rearing and stereotypy. This study aims to reveal the possible antipsychotic and oxidative effects of omega-3 fatty acids by comparing with chlorpromazine, a conventional antipsychotic drug, through evaluating the novelty-induced rearing and apomorphine-induced stereotypic behaviors, as well as malondialdehyde and glutathione levels in rats. METHODS Twenty-eight, adult, male, Wistar rats were used in the study. Briefly, 4 groups of rats (n = 7) were administered docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) (300 mg/kg; DHA: 120 mg/kg + EPA: 180 mg/kg intraperitoneally [IP]), DHA + EPA (150 mg/kg; DHA: 60 mg/kg + EPA: 90 mg/kg IP), chlorpromazine (1 mg/kg, IP) and isotonic saline (1 mL/kg, IP). One hour later, apomorphine (2 mg/kg, subcutaneously) was administered to each rat. After the apomorphine administration, rats were observed for stereotypic behavior. RESULTS This study shows that omega-3 fatty acids, "similar to antipsychotics," reversed the psychotic like effects, increase of oxidants and decrease of antioxidants that are composed experimentally in rats. CONCLUSIONS The application of omega-3 fatty acids has antipsychotic effects and causes an oxidative imbalance. This study adds new evidence to the current literature regarding the possible antipsychotic effects of omega-3 fatty acids.
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46
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Essential role of docosahexaenoic acid towards development of a smarter brain. Neurochem Int 2015; 89:51-62. [DOI: 10.1016/j.neuint.2015.08.014] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2015] [Revised: 08/18/2015] [Accepted: 08/26/2015] [Indexed: 01/25/2023]
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Dietary supplementation with n-3 fatty acids from weaning limits brain biochemistry and behavioural changes elicited by prenatal exposure to maternal inflammation in the mouse model. Transl Psychiatry 2015; 5:e641. [PMID: 26393487 PMCID: PMC5068805 DOI: 10.1038/tp.2015.126] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2015] [Revised: 07/02/2015] [Accepted: 07/22/2015] [Indexed: 12/15/2022] Open
Abstract
Prenatal exposure to maternal immune activation (MIA) increases the risk of schizophrenia and autism in the offspring. The MIA rodent model provides a valuable tool to directly test the postnatal consequences of exposure to an early inflammatory insult; and examine novel preventative strategies. Here we tested the hypotheses that behavioural differences in the MIA mouse model are accompanied by in vivo and ex vivo alterations in brain biochemistry; and that these can be prevented by a post-weaning diet enriched with n-3 polyunsaturated fatty acid (PUFA). The viral analogue PolyI:C (POL) or saline (SAL) was administered to pregnant mice on gestation day 9. Half the resulting male offspring (POL=21; SAL=17) were weaned onto a conventional lab diet (n-6 PUFA); half were weaned onto n-3 PUFA-enriched diet. In vivo magnetic resonance spectroscopy measures were acquired prior to behavioural tests; glutamic acid decarboxylase 67 (GAD67) and tyrosine hydroxylase protein levels were measured ex vivo. The main findings were: (i) Adult MIA-exposed mice fed a standard diet had greater N-acetylaspartate/creatine (Cr) and lower myo-inositol/Cr levels in the cingulate cortex in vivo. (ii) The extent of these metabolite differences was correlated with impairment in prepulse inhibition. (iii) MIA-exposed mice on the control diet also had higher levels of anxiety and altered levels of GAD67 ex vivo. (iv) An n-3 PUFA diet prevented all the in vivo and ex vivo effects of MIA observed. Thus, n-3 PUFA dietary enrichment from early life may offer a relatively safe and non-toxic approach to limit the otherwise persistent behavioural and biochemical consequences of prenatal exposure to inflammation. This result may have translational importance.
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Zugno AI, Pacheco FD, Budni J, de Oliveira MB, Canever L, Heylmann AS, Wessler PG, da Rosa Silveira F, Mastella GA, Gonçalves CL, Freitas KV, de Castro AA, Streck EL, Quevedo J. Maternal deprivation disrupts mitochondrial energy homeostasis in the brain of rats subjected to ketamine-induced schizophrenia. Metab Brain Dis 2015; 30:1043-53. [PMID: 25920483 DOI: 10.1007/s11011-015-9671-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2014] [Accepted: 04/12/2015] [Indexed: 02/04/2023]
Abstract
Maternal deprivation (MD) appears to be one of the environmental factors involved in the pathophysiology of schizophrenia. A widely used animal model of the schizophrenia involves the administration of ketamine, a dissociative anesthetic, NMDA receptors noncompetitive antagonist, that induce symptoms such as schizophrenia. To clarify the molecular mechanism of schizophrenia induced by MD, we investigated alterations in energetic metabolism, oxidative stress and neurotrophic factor levels in the brain of rats following MD and/or a single administration of ketamine during adulthood. Male Wistar rats were subjected to MD for 10 days. Additionally, these animals received acute ketamine (5, 15 or 25 mg/kg by intraperitoneal route, i.p.) during adulthood, and 30 min later, they were killed and the prefrontal cortex (PFC), the hippocampus and the striatum were removed for molecular analyses. Ketamine 25 mg/kg and/or MD and Ketamine 15 and 5 mg/kg with MD decreased the creatine kinase (CK) activity in the hippocampus. The enzyme activity of succinate dehydrogenase (SDH) in the Krebs cycle had increased in the striatum following the administration of ketamine 25 mg/kg, MD per se or MD plus ketamine 5 and 15 mg/kg. MD per se or MD combined with ketamine in different doses increased the activity of mitochondrial complexes. The PFC of animals subjected to MD and administered with ketamine 5 mg/kg exhibited increased protein carbonyl content. In the hippocampus, ketamine 15 mg/kg, ketamine 25 mg/kg and MD each increased the carbonyl content. In the striatum, the TBARS levels were increased by the administration of ketamine 25 mg/kg. Finally, in the hippocampus, MD alone or in combination with ketamine reduced the Nerve Growth Factor (NGF) levels; however, the Brain-derived Neurotrophic Factor (BDNF) levels were unaltered. In the present study, we suggest that MD increased the risk of psychotic symptoms in adulthood, altering different parameters of energy and oxidative stress. Our results suggest that adverse experiences occurring early in life may sensitize specific neurocircuits to subsequent stressors, inducing vulnerability, and may help us understand the pathophysiological mechanisms involved in this disorder.
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Affiliation(s)
- Alexandra Ioppi Zugno
- Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil,
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Do KQ, Cuenod M, Hensch TK. Targeting Oxidative Stress and Aberrant Critical Period Plasticity in the Developmental Trajectory to Schizophrenia. Schizophr Bull 2015; 41:835-46. [PMID: 26032508 PMCID: PMC4466197 DOI: 10.1093/schbul/sbv065] [Citation(s) in RCA: 125] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Schizophrenia is a neurodevelopmental disorder reflecting a convergence of genetic risk and early life stress. The slow progression to first psychotic episode represents both a window of vulnerability as well as opportunity for therapeutic intervention. Here, we consider recent neurobiological insight into the cellular and molecular components of developmental critical periods and their vulnerability to redox dysregulation. In particular, the consistent loss of parvalbumin-positive interneuron (PVI) function and their surrounding perineuronal nets (PNNs) as well as myelination in patient brains is consistent with a delayed or extended period of circuit instability. This linkage to critical period triggers (PVI) and brakes (PNN, myelin) implicates mistimed trajectories of brain development in mental illness. Strategically introduced antioxidant treatment or later reinforcement of molecular brakes may then offer a novel prophylactic psychiatry.
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Affiliation(s)
- Kim Q. Do
- Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital-CHUV, Prilly-Lausanne, Switzerland
| | - Michel Cuenod
- Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital-CHUV, Prilly-Lausanne, Switzerland
| | - Takao K. Hensch
- Center for Brain Science, Department of Molecular Cellular Biology, Harvard University, Cambridge, MA,*To whom correspondence should be addressed; Center for Brain Science, Department of Molecular Cellular Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138, US; tel: +1-617-384-5882; fax: +1-617-495-4038; e-mail:
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50
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Pawełczyk T, Grancow M, Kotlicka-Antczak M, Trafalska E, Gębski P, Szemraj J, Żurner N, Pawełczyk A. Omega-3 fatty acids in first-episode schizophrenia - a randomized controlled study of efficacy and relapse prevention (OFFER): rationale, design, and methods. BMC Psychiatry 2015; 15:97. [PMID: 25934131 PMCID: PMC4456694 DOI: 10.1186/s12888-015-0473-2] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2014] [Accepted: 04/20/2015] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Polyunsaturated fatty acid (PUFA) metabolism abnormalities have been long implicated in the etiology of schizophrenia. Although several randomized clinical trials have been carried out to assess the efficacy of omega-3 PUFA as add-on therapy in reducing psychopathology in populations of chronic patients with schizophrenia, only a few concern first-episode schizophrenia. The majority of these studies used a 12-week intervention based on ethyl-eicosapentaenoic acid (ethyl-EPA), however, with conflicting results. An intervention based on docosahexaenoic acid plus EPA has not been used in first-episode schizophrenia studies so far. No add-on supplementation studies have been carried out in medicated first-episode schizophrenia patients to assess the efficacy of omega-3 PUFA in preventing relapses. METHODS A randomized placebo-controlled one-center trial will be used to compare the efficacy of 26-week intervention, composed of either 1320 mg/day of EPA and 880 mg/day of DHA, or olive oil placebo with regard to symptom severity and relapse rate in first-episode schizophrenia patients. Eighty-two patients (aged 16-35) will be recruited for the study. Eligible patients will be randomly allocated to one of two intervention arms: an active arm or a placebo arm (olive oil). The primary outcome measure of the clinical evaluation is schizophrenia symptom severity measured by the Positive and Negative Syndrome Scale (PANSS). Other outcomes include depressive symptoms, patient functioning and the level of insight. Correlates of change measured during the study will include structural brain changes, oxidative stress and defense, as well as neuroplasticity indicators. Metabolic syndrome components will also be assessed throughout the study. DISCUSSION By comparing 26-week administration of EPA + DHA or (placebo) olive oil as add-on therapy in reducing symptom severity and one-year relapse rate in patients with first episode schizophrenia, it is intended to provide new insights into the efficacy of omega-3 PUFA and correlates of change, and contribute to the improvement of mental health care for individuals suffering from schizophrenia. TRIAL REGISTRATION This study has been registered at Clinical Trials.gov with the following number: NCT02210962 .
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Affiliation(s)
- Tomasz Pawełczyk
- Department of Affective and Psychotic Disorders, Medical University of Lodz, ul. Czechoslowacka 8/10, 92-216, Lodz, Poland.
| | - Marta Grancow
- Central Teaching Hospital, Medical University of Lodz, ul. Pomorska 251, 92-213, Lodz, Poland.
| | - Magdalena Kotlicka-Antczak
- Department of Affective and Psychotic Disorders, Medical University of Lodz, ul. Czechoslowacka 8/10, 92-216, Lodz, Poland.
| | - Elżbieta Trafalska
- Department of Nutrition Hygiene and Epidemiology, Medical University of Lodz, ul. Jaracza 63, 90-251, Lodz, Poland.
| | - Piotr Gębski
- Scanlab Medical Diagnostics, ul. Przedzalniana 66, 90-338, Lodz, Poland.
| | - Janusz Szemraj
- Department of Medical Biochemistry, Medical University of Lodz, ul. Czechoslowacka 8/10, 92-216, Lodz, Poland.
| | - Natalia Żurner
- Clinical Psychology Resident in the Department of Affective and Psychotic Disorders, Medical University of Lodz, Lodz, Poland.
| | - Agnieszka Pawełczyk
- Department of Affective and Psychotic Disorders, Medical University of Lodz, ul. Czechoslowacka 8/10, 92-216, Lodz, Poland.
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