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White TA, Miller SL, Sutherland AE, Allison BJ, Camm EJ. Perinatal compromise affects development, form, and function of the hippocampus part one; clinical studies. Pediatr Res 2024; 95:1698-1708. [PMID: 38519794 PMCID: PMC11245394 DOI: 10.1038/s41390-024-03105-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 01/30/2024] [Accepted: 02/05/2024] [Indexed: 03/25/2024]
Abstract
The hippocampus is a neuron-rich specialised brain structure that plays a central role in the regulation of emotions, learning and memory, cognition, spatial navigation, and motivational processes. In human fetal development, hippocampal neurogenesis is principally complete by mid-gestation, with subsequent maturation comprising dendritogenesis and synaptogenesis in the third trimester of pregnancy and infancy. Dendritogenesis and synaptogenesis underpin connectivity. Hippocampal development is exquisitely sensitive to perturbations during pregnancy and at birth. Clinical investigations demonstrate that preterm birth, fetal growth restriction (FGR), and acute hypoxic-ischaemic encephalopathy (HIE) are common perinatal complications that alter hippocampal development. In turn, deficits in hippocampal development and structure mediate a range of neurodevelopmental disorders, including cognitive and learning problems, autism, and Attention-Deficit/Hyperactivity Disorder (ADHD). In this review, we summarise the developmental profile of the hippocampus during fetal and neonatal life and examine the hippocampal deficits observed following common human pregnancy complications. IMPACT: The review provides a comprehensive summary of the developmental profile of the hippocampus in normal fetal and neonatal life. We address a significant knowledge gap in paediatric research by providing a comprehensive summary of the relationship between pregnancy complications and subsequent hippocampal damage, shedding new light on this critical aspect of early neurodevelopment.
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Affiliation(s)
- Tegan A White
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia.
- Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia.
| | - Suzanne L Miller
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia
- Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia
| | - Amy E Sutherland
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia
- Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia
| | - Beth J Allison
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia
- Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia
| | - Emily J Camm
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia.
- Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia.
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2
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Todorovic S, Simeunovic V, Prvulovic M, Dakic T, Jevdjovic T, Sokanovic S, Kanazir S, Mladenovic A. Dietary restriction alters insulin signaling pathway in the brain. Biofactors 2024; 50:450-466. [PMID: 37975613 DOI: 10.1002/biof.2018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 09/07/2023] [Indexed: 11/19/2023]
Abstract
Insulin is known to be a key hormone in the regulation of peripheral glucose homeostasis, but beyond that, its effects on the brain are now undisputed. Impairments in insulin signaling in the brain, including changes in insulin levels, are thought to contribute significantly to declines in cognitive performance, especially during aging. As one of the most widely studied experimental interventions, dietary restriction (DR) is considered to delay the neurodegenerative processes associated with aging. Recently, however, data began to suggest that the onset and duration of a restrictive diet play a critical role in the putative beneficial outcome. Because the effects of DR on insulin signaling in the brain have been poorly studied, we decided to examine the effects of DR that differed in onset and duration: long-term DR (LTDR), medium-term DR (MTDR), and short-term DR (STDR) on the expression of proteins involved in insulin signaling in the hippocampus of 18- and 24-month-old male Wistar rats. We found that DR-induced changes in insulin levels in the brain may be independent of what happens in the periphery after restricted feeding. Significantly changed insulin content in the hippocampus, together with altered insulin signaling were found under the influence of DR, but the outcome was highly dependent on the onset and duration of DR.
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Affiliation(s)
- Smilja Todorovic
- Department for Neurobiology, Institute for Biological Research "Sinisa Stankovic", National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Valentina Simeunovic
- Department for Neurobiology, Institute for Biological Research "Sinisa Stankovic", National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Milica Prvulovic
- Department for Neurobiology, Institute for Biological Research "Sinisa Stankovic", National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Tamara Dakic
- Department for Comparative Physiology and Ecophysiology, Institute for Physiology and Biochemistry "Ivan Djaja", Faculty of Biology, University of Belgrade, Belgrade, Serbia
| | - Tanja Jevdjovic
- Department for Comparative Physiology and Ecophysiology, Institute for Physiology and Biochemistry "Ivan Djaja", Faculty of Biology, University of Belgrade, Belgrade, Serbia
| | - Srdjan Sokanovic
- Department for Neurobiology, Institute for Biological Research "Sinisa Stankovic", National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Selma Kanazir
- Department for Neurobiology, Institute for Biological Research "Sinisa Stankovic", National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Aleksandra Mladenovic
- Department for Neurobiology, Institute for Biological Research "Sinisa Stankovic", National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
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3
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Cogut V, McNeely TL, Bussian TJ, Graves SI, Baker DJ. Caloric Restriction Improves Spatial Learning Deficits in Tau Mice. J Alzheimers Dis 2024; 98:925-940. [PMID: 38517786 PMCID: PMC11068089 DOI: 10.3233/jad-231117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/24/2024]
Abstract
Background Caloric restriction (CR) has been recognized for its benefits in delaying age-related diseases and extending lifespan. While its effects on amyloid pathology in Alzheimer's disease (AD) mouse models are well-documented, its effects on tauopathy, another hallmark of AD, are less explored. Objective To assess the impact of a short-term 30% CR regimen on age-dependent spatial learning deficits and pathological features in a tauopathy mouse model. Methods We subjected male PS19 tau P301S (hereafter PS19) and age-matched wildtype mice from two age cohorts (4.5 and 7.5 months old) to a 6-week 30% CR regimen. Spatial learning performance was assessed using the Barnes Maze test. Tau pathology, neuroinflammation, hippocampal cell proliferation, and neurogenesis were evaluated in the older cohort by immunohistochemical staining and RT-qPCR. Results CR mitigated age-dependent spatial learning deficits in PS19 mice but exhibited limited effects on tau pathology and the associated neuroinflammation. Additionally, we found a decrease in hippocampal cell proliferation, predominantly of Iba1+ cells. Conclusions Our findings reinforce the cognitive benefits conferred by CR despite its limited modulation of disease pathology. Given the pivotal role of microglia in tau-driven pathology, the observed reduction in Iba1+ cells under CR suggests potential therapeutic implications, particularly if CR would be introduced early in disease progression.
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Affiliation(s)
- Valeria Cogut
- Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
| | - Taylor L. McNeely
- Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
| | - Tyler J. Bussian
- Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
| | - Sara I. Graves
- Department of Pediatric and Adolescent Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
| | - Darren J. Baker
- Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
- Department of Pediatric and Adolescent Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
- Paul F. Glenn Center for Biology of Aging Research at Mayo Clinic, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
- Robert and Arlene Kogod Center on Aging, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
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4
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Marzola P, Melzer T, Pavesi E, Gil-Mohapel J, Brocardo PS. Exploring the Role of Neuroplasticity in Development, Aging, and Neurodegeneration. Brain Sci 2023; 13:1610. [PMID: 38137058 PMCID: PMC10741468 DOI: 10.3390/brainsci13121610] [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: 10/23/2023] [Revised: 11/16/2023] [Accepted: 11/18/2023] [Indexed: 12/24/2023] Open
Abstract
Neuroplasticity refers to the ability of the brain to reorganize and modify its neural connections in response to environmental stimuli, experience, learning, injury, and disease processes. It encompasses a range of mechanisms, including changes in synaptic strength and connectivity, the formation of new synapses, alterations in the structure and function of neurons, and the generation of new neurons. Neuroplasticity plays a crucial role in developing and maintaining brain function, including learning and memory, as well as in recovery from brain injury and adaptation to environmental changes. In this review, we explore the vast potential of neuroplasticity in various aspects of brain function across the lifespan and in the context of disease. Changes in the aging brain and the significance of neuroplasticity in maintaining cognitive function later in life will also be reviewed. Finally, we will discuss common mechanisms associated with age-related neurodegenerative processes (including protein aggregation and accumulation, mitochondrial dysfunction, oxidative stress, and neuroinflammation) and how these processes can be mitigated, at least partially, by non-invasive and non-pharmacologic lifestyle interventions aimed at promoting and harnessing neuroplasticity.
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Affiliation(s)
- Patrícia Marzola
- Department of Morphological Sciences and Graduate Neuroscience Program, Center of Biological Sciences, Federal University of Santa Catarina, Florianopolis 88040-900, SC, Brazil; (P.M.); (T.M.); (E.P.)
| | - Thayza Melzer
- Department of Morphological Sciences and Graduate Neuroscience Program, Center of Biological Sciences, Federal University of Santa Catarina, Florianopolis 88040-900, SC, Brazil; (P.M.); (T.M.); (E.P.)
| | - Eloisa Pavesi
- Department of Morphological Sciences and Graduate Neuroscience Program, Center of Biological Sciences, Federal University of Santa Catarina, Florianopolis 88040-900, SC, Brazil; (P.M.); (T.M.); (E.P.)
| | - Joana Gil-Mohapel
- Division of Medical Sciences, University of Victoria, Victoria, BC V8P 5C2, Canada
- Island Medical Program, Faculty of Medicine, University of British Columbia, Victoria, BC V8P 5C2, Canada
| | - Patricia S. Brocardo
- Department of Morphological Sciences and Graduate Neuroscience Program, Center of Biological Sciences, Federal University of Santa Catarina, Florianopolis 88040-900, SC, Brazil; (P.M.); (T.M.); (E.P.)
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Kim SR, Eom Y, Lee SH. Comprehensive analysis of sex differences in the function and ultrastructure of hippocampal presynaptic terminals. Neurochem Int 2023; 169:105570. [PMID: 37451344 DOI: 10.1016/j.neuint.2023.105570] [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: 01/25/2023] [Revised: 05/08/2023] [Accepted: 07/04/2023] [Indexed: 07/18/2023]
Abstract
Sex differences in the brain, encompassing variations in specific brain structures, size, cognitive function, and synaptic connections, have been identified across numerous species. While previous research has explored sex differences in postsynaptic structures, synaptic plasticity, and hippocampus-dependent functions, the hippocampal presynaptic terminals remain largely uninvestigated. The hippocampus is a critical structure responsible for multiple brain functions. This study examined presynaptic differences in cultured hippocampal neurons derived from male and female mice using a combination of biochemical assays, functional analyses measuring exocytosis and endocytosis of synaptic vesicle proteins, ultrastructural analyses via electron microscopy, and presynaptic Ca2+-specific optical probes. Our findings revealed that female neurons exhibited a higher number of synaptic vesicles at presynaptic terminals compared to male neurons. However, no significant differences were observed in presynaptic protein expression, presynaptic terminal ultrastructure, synaptic vesicle exocytosis and endocytosis, or presynaptic Ca2+ alterations between male and female neurons.
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Affiliation(s)
- Sung Rae Kim
- College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea; Brain Research Core Facilities of Korea Brain Research Institute (KBRI), Daegu 41068, Republic of Korea.
| | - Yunkyung Eom
- College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.
| | - Sung Hoon Lee
- College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.
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6
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Gupta M, Pandey S, Rumman M, Singh B, Mahdi AA. Molecular mechanisms underlying hyperglycemia associated cognitive decline. IBRO Neurosci Rep 2023; 14:57-63. [PMID: 36590246 PMCID: PMC9800261 DOI: 10.1016/j.ibneur.2022.12.006] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 12/10/2022] [Indexed: 12/14/2022] Open
Abstract
Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia. DM can lead to a number of secondary complications affecting multiple organs in the body including the eyes, kidney, heart, and brain. The most common effect of hyperglycemia on the brain is cognitive decline. It has been estimated that 20-70% of people with DM have cognitive deficits. High blood sugar affects key brain areas involved in learning, memory, and spatial navigation, and the structural complexity of the brain has made it prone to a variety of pathological disorders, including T2DM. Studies have reported that cognitive decline can occur in people with diabetes, which could go undetected for several years. Moreover, studies on brain imaging suggest extensive effects on different brain regions in patients with T2D. It remains unclear whether diabetes-associated cognitive decline is a consequence of hyperglycemia or a complication that co-occurs with T2D. The exact mechanism underlying cognitive impairment in diabetes is complex; however, impaired glucose metabolism and abnormal insulin function are thought to play important roles. In this review, we have tried to summarize the effect of hyperglycemia on the brain structure and functions, along with the potential mechanisms underlying T2DM-associated cognitive decline.
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Affiliation(s)
- Mrinal Gupta
- Department of Biochemistry, King George’s Medical University, Lucknow, Uttar Pradesh, India
| | - Shivani Pandey
- Department of Biochemistry, King George’s Medical University, Lucknow, Uttar Pradesh, India
| | - Mohammad Rumman
- Department of Biochemistry, King George’s Medical University, Lucknow, Uttar Pradesh, India
| | - Babita Singh
- Department of Biochemistry, King George’s Medical University, Lucknow, Uttar Pradesh, India
| | - Abbas Ali Mahdi
- Department of Biochemistry, King George’s Medical University, Lucknow, Uttar Pradesh, India
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Pisani A, Paciello F, Del Vecchio V, Malesci R, De Corso E, Cantone E, Fetoni AR. The Role of BDNF as a Biomarker in Cognitive and Sensory Neurodegeneration. J Pers Med 2023; 13:jpm13040652. [PMID: 37109038 PMCID: PMC10140880 DOI: 10.3390/jpm13040652] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 04/04/2023] [Accepted: 04/08/2023] [Indexed: 04/29/2023] Open
Abstract
Brain-derived neurotrophic factor (BDNF) has a crucial function in the central nervous system and in sensory structures including olfactory and auditory systems. Many studies have highlighted the protective effects of BDNF in the brain, showing how it can promote neuronal growth and survival and modulate synaptic plasticity. On the other hand, conflicting data about BDNF expression and functions in the cochlear and in olfactory structures have been reported. Several clinical and experimental research studies showed alterations in BDNF levels in neurodegenerative diseases affecting the central and peripheral nervous system, suggesting that BDNF can be a promising biomarker in most neurodegenerative conditions, including Alzheimer's disease, shearing loss, or olfactory impairment. Here, we summarize current research concerning BDNF functions in brain and in sensory domains (olfaction and hearing), focusing on the effects of the BDNF/TrkB signalling pathway activation in both physiological and pathological conditions. Finally, we review significant studies highlighting the possibility to target BDNF as a biomarker in early diagnosis of sensory and cognitive neurodegeneration, opening new opportunities to develop effective therapeutic strategies aimed to counteract neurodegeneration.
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Affiliation(s)
- Anna Pisani
- Department of Otolaryngology Head and Neck Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Fabiola Paciello
- Department of Neuroscience, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Valeria Del Vecchio
- Department of Neuroscience, Reproductive Sciences and Dentistry-Audiology Section, University of Naples Federico II, 80131 Naples, Italy
| | - Rita Malesci
- Department of Neuroscience, Reproductive Sciences and Dentistry-Audiology Section, University of Naples Federico II, 80131 Naples, Italy
| | - Eugenio De Corso
- Department of Otolaryngology Head and Neck Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Elena Cantone
- Department of Neuroscience, Reproductive Sciences and Dentistry-ENT Section, University of Naples Federico II, 80131 Naples, Italy
| | - Anna Rita Fetoni
- Department of Neuroscience, Reproductive Sciences and Dentistry-Audiology Section, University of Naples Federico II, 80131 Naples, Italy
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8
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Dutra ML, Dias P, Freiberger V, Ventura L, Comim CM, Martins DF, Bobinski F. Maternal immune activation induces autism-like behavior and reduces brain-derived neurotrophic factor levels in the hippocampus and offspring cortex of C57BL/6 mice. Neurosci Lett 2023; 793:136974. [PMID: 36414133 DOI: 10.1016/j.neulet.2022.136974] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 11/10/2022] [Accepted: 11/17/2022] [Indexed: 11/21/2022]
Abstract
Prenatal factors such as viral or bacterial infections occurring mainly during the first trimesters of pregnancy can increase the incidence of autism spectrum disorder (ASD) in children. In an animal model, it is already known that maternal immune activation (MIA) induces autistic-like behavior. However, it is unclear whether this behavior presents itself in young animals. In this preclinical experimental study, we investigated in the offspring of C57BL/6 female mice submitted to MIA with lipopolysaccharide (LPS), typically altered behaviors in ASD, such as social interaction and stereotyped self-grooming movement, as well as the levels of the brain-derived neurotrophic factor (BDNF) and interleukin 17A (IL-17A) in the hippocampus and cortex, at 28 and 60 days. Adult animals aged 60 days, offspring of females submitted to MIA, showed a decrease in the time of social interaction and an increase in the number of self-cleaning movements. In the hippocampus of the offspring of females submitted to MIA, a decrease in BDNF levels was found at 28 days and 60 days of life, and a decrease in IL-17A levels only at 60 days. The levels of BDNF and IL-17A did not change in the cortex of the offspring of mice submitted to MIA at the evaluated times. Young animals aged 28 days still showed typical behavior, without social deficits and stereotyped movements that characterize ASD, which suggests that at this age it is still not possible to observe the repercussions of MIA in this model. In the neurochemical issues of the hippocampal region, impairment of BDNF levels has already been demonstrated, which may be an important factor for the observation of ASD-like behaviors in adult mice at 60 days.
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Affiliation(s)
- Matheus Luchini Dutra
- Experimental Neuroscience Laboratory (LaNEx), Postgraduate Program in Health Sciences, University of Southern Santa Catarina (UNISUL), Palhoça, 88137-270 Santa Catarina, Brazil; Research Group in Neurodevelopment of Childhood and Adolescence, Laboratory of Experimental Neuroscience, Postgraduate Program in Health Sciences, UNISUL, Palhoça, 88137-270 Santa Catarina, Brazil
| | - Paula Dias
- Experimental Neuroscience Laboratory (LaNEx), Postgraduate Program in Health Sciences, University of Southern Santa Catarina (UNISUL), Palhoça, 88137-270 Santa Catarina, Brazil; Research Group in Neurodevelopment of Childhood and Adolescence, Laboratory of Experimental Neuroscience, Postgraduate Program in Health Sciences, UNISUL, Palhoça, 88137-270 Santa Catarina, Brazil
| | - Viviane Freiberger
- Experimental Neuroscience Laboratory (LaNEx), Postgraduate Program in Health Sciences, University of Southern Santa Catarina (UNISUL), Palhoça, 88137-270 Santa Catarina, Brazil; Research Group in Neurodevelopment of Childhood and Adolescence, Laboratory of Experimental Neuroscience, Postgraduate Program in Health Sciences, UNISUL, Palhoça, 88137-270 Santa Catarina, Brazil
| | - Leticia Ventura
- Experimental Neuroscience Laboratory (LaNEx), Postgraduate Program in Health Sciences, University of Southern Santa Catarina (UNISUL), Palhoça, 88137-270 Santa Catarina, Brazil; Research Group in Neurodevelopment of Childhood and Adolescence, Laboratory of Experimental Neuroscience, Postgraduate Program in Health Sciences, UNISUL, Palhoça, 88137-270 Santa Catarina, Brazil
| | - Clarissa Martinelli Comim
- Research Group in Neurodevelopment of Childhood and Adolescence, Laboratory of Experimental Neuroscience, Postgraduate Program in Health Sciences, UNISUL, Palhoça, 88137-270 Santa Catarina, Brazil
| | - Daniel Fernandes Martins
- Experimental Neuroscience Laboratory (LaNEx), Postgraduate Program in Health Sciences, University of Southern Santa Catarina (UNISUL), Palhoça, 88137-270 Santa Catarina, Brazil
| | - Franciane Bobinski
- Experimental Neuroscience Laboratory (LaNEx), Postgraduate Program in Health Sciences, University of Southern Santa Catarina (UNISUL), Palhoça, 88137-270 Santa Catarina, Brazil.
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9
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Melgar-Locatelli S, de Ceglia M, Mañas-Padilla MC, Rodriguez-Pérez C, Castilla-Ortega E, Castro-Zavala A, Rivera P. Nutrition and adult neurogenesis in the hippocampus: Does what you eat help you remember? Front Neurosci 2023; 17:1147269. [PMID: 36908779 PMCID: PMC9995971 DOI: 10.3389/fnins.2023.1147269] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 02/06/2023] [Indexed: 02/25/2023] Open
Abstract
Neurogenesis is a complex process by which neural progenitor cells (NPCs)/neural stem cells (NSCs) proliferate and differentiate into new neurons and other brain cells. In adulthood, the hippocampus is one of the areas with more neurogenesis activity, which is involved in the modulation of both emotional and cognitive hippocampal functions. This complex process is affected by many intrinsic and extrinsic factors, including nutrition. In this regard, preclinical studies performed in rats and mice demonstrate that high fats and/or sugars diets have a negative effect on adult hippocampal neurogenesis (AHN). In contrast, diets enriched with bioactive compounds, such as polyunsaturated fatty acids and polyphenols, as well as intermittent fasting or caloric restriction, can induce AHN. Interestingly, there is also growing evidence demonstrating that offspring AHN can be affected by maternal nutrition in the perinatal period. Therefore, nutritional interventions from early stages and throughout life are a promising perspective to alleviate neurodegenerative diseases by stimulating neurogenesis. The underlying mechanisms by which nutrients and dietary factors affect AHN are still being studied. Interestingly, recent evidence suggests that additional peripheral mediators may be involved. In this sense, the microbiota-gut-brain axis mediates bidirectional communication between the gut and the brain and could act as a link between nutritional factors and AHN. The aim of this mini-review is to summarize, the most recent findings related to the influence of nutrition and diet in the modulation of AHN. The importance of maternal nutrition in the AHN of the offspring and the role of the microbiota-gut-brain axis in the nutrition-neurogenesis relationship have also been included.
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Affiliation(s)
- Sonia Melgar-Locatelli
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain.,Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain
| | - Marialuisa de Ceglia
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain.,UGC Salud Mental, Hospital Universitario Regional de Málaga, Málaga, Spain
| | - M Carmen Mañas-Padilla
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain.,Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain
| | - Celia Rodriguez-Pérez
- Departamento de Nutrición y Bromatología, Facultad de Ciencias de la Salud, Universidad de Granada, Granada, Spain.,Instituto de Nutrición y Tecnología de los Alimentos 'José Mataix', Universidad de Granada, Granada, Spain.,Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain
| | - Estela Castilla-Ortega
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain.,Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain
| | - Adriana Castro-Zavala
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain.,Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain
| | - Patricia Rivera
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain.,UGC Salud Mental, Hospital Universitario Regional de Málaga, Málaga, Spain
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10
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Lods M, Mortessagne P, Pacary E, Terral G, Farrugia F, Mazier W, Masachs N, Charrier V, Cota D, Ferreira G, Abrous DN, Tronel S. Chemogenetic stimulation of adult neurogenesis, and not neonatal neurogenesis, is sufficient to improve long-term memory accuracy. Prog Neurobiol 2022; 219:102364. [DOI: 10.1016/j.pneurobio.2022.102364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 09/21/2022] [Accepted: 10/06/2022] [Indexed: 12/05/2022]
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11
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Walrath T, McMahan RH, Idrovo JP, Quillinan N, Kovacs EJ. Cutaneous burn injury induces neuroinflammation and reactive astrocyte activation in the hippocampus of aged mice. Exp Gerontol 2022; 169:111975. [PMID: 36208823 DOI: 10.1016/j.exger.2022.111975] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Revised: 09/29/2022] [Accepted: 09/30/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND By 2050, one in six people globally will be 65 or older. Confusion and delirium are significant complications after burn injury, especially in the elderly population. The etiology is still unknown, however complications may be driven by pro-inflammatory activation of astrocytes within the hippocampus (HPC) after burn injury. Reduced levels of phosphorylated cyclic-AMP response binding element (pCREB), caused by elevated systemic pro-inflammatory cytokines, could lead to cognitive decline and memory impairment. METHODS To examine the effects of remote injury on neuroinflammation in advanced age, young and aged mice were subjected to a 15 % total body surface area scald burn or sham injury, and euthanized after 24 h. Expression of ccl2 and tnfa were measured by qPCR in the whole brain and HPC. Astrocyte activation was measured by immunofluorescence within the HPC. pCREB was measured by immunohistochemistry in the dentate gyrus. RESULTS We saw an 80-fold increase in ccl2 and a 30-fold elevation in tnfa after injury in the whole brain of aged mice compared to young groups and aged sham mice (p < 0.05 and p < 0.05, respectively). Additionally, there was a 30-fold increase in ccl2 within isolated HPC of aged injured mice when compared to sham injured animals (p < 0.05). When investigating specific HPC regions, immunofluorescence staining showed a >20 % rise in glial fibrillary acidic protein (GFAP) positive astrocytes within the cornu ammonis 3 (CA3) of aged injured mice when compared to all other groups (p < 0.05). Lastly, we observed a >20 % decrease in pCREB staining by immunohistochemistry in the dentate gyrus of aged mice compared to young regardless of injury (p < 0.05). CONCLUSIONS These novel data suggest that remote injury in aged, but not young, mice is associated with neuroinflammation and astrocyte activation within the HPC. These factors, paired with an age related reduction in pCREB, could help explain the increased cognitive decline seen in burn patients of advanced age. To our knowledge, we are the first group to examine the impact of advanced age combined with burn injury on inflammation and astrocyte activation within the brain.
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Affiliation(s)
- Travis Walrath
- Department of Surgery, Division of GI, Trauma, and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States of America
| | - Rachel H McMahan
- Department of Surgery, Division of GI, Trauma, and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States of America
| | - Juan-Pablo Idrovo
- Department of Surgery, Division of GI, Trauma, and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States of America
| | - Nidia Quillinan
- Department of Anesthesiology, Neuronal Injury Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Elizabeth J Kovacs
- Department of Surgery, Division of GI, Trauma, and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States of America.
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12
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Verma V, Kumari R, Singaravel M. Chronic altered light-dark cycle differentially affects hippocampal CA1 and DG neuronal arborization in diurnal and nocturnal rodents. Chronobiol Int 2022; 39:665-677. [PMID: 34983277 DOI: 10.1080/07420528.2021.2023561] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The hippocampus, an extension of the temporal part of the cerebral cortex, plays a crucial role in learning and memory. Structural and functional complexity within the hippocampus is greatly affected by a variety of external environmental stimuli including alteration in the light-dark (LD) cycle. The effect of altered LD cycle in learning and memory associated cognitive impairment has been reported in rodents. However, a comparative study of underlying neuronal changes between nocturnal and diurnal species is not well explored. The objective of the present study was to explore the morphological changes in hippocampal CA1 and DG neurons in response to prolonged constant condition viz. constant light (LL) and constant darkness (DD) in diurnal squirrels and nocturnal mice. Animals (n = 5/group) were placed in chronocubicle under 12:12 h LD, LL and DD. After four weeks, brain tissues were collected and processed for Golgi-Cox staining to analyze morphological changes in CA1 and DG neurons. The total and basal dendritic length, basal dendrite number, branch end, the diameter of apical dendrite and spine density were analyzed. The results showed a significant reduction in structural complexity of CA1 and DG neurons of squirrels exposed to prolonged constant darkness, whereas mice showed a significant increase as compared to LD. However, a significantly reduced neuronal complexity was observed in both squirrels and mice exposed to prolonged constant light. The results obtained were further confirmed by Sholl analysis of CA1 and DG neurons. The present study suggests that prolonged constant light may cause adverse effects on the neuronal complexity of both diurnal and nocturnal animals, but constant darkness may cause adverse effects mainly to the diurnal animals.
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Affiliation(s)
- Vivek Verma
- Chronobiology Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, India
| | - Ruchika Kumari
- Chronobiology Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, India
| | - Muniyandi Singaravel
- Chronobiology Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, India
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13
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Chiavellini P, Canatelli-Mallat M, Lehmann M, Goya RG, Morel GR. Therapeutic potential of glial cell line-derived neurotrophic factor and cell reprogramming for hippocampal-related neurological disorders. Neural Regen Res 2022; 17:469-476. [PMID: 34380873 PMCID: PMC8504380 DOI: 10.4103/1673-5374.320966] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Hippocampus serves as a pivotal role in cognitive and emotional processes, as well as in the regulation of the hypothalamus-pituitary axis. It is known to undergo mild neurodegenerative changes during normal aging and severe atrophy in Alzheimer’s disease. Furthermore, dysregulation in the hippocampal function leads to epilepsy and mood disorders. In the first section, we summarized the most salient knowledge on the role of glial cell-line-derived neurotrophic factor and its receptors focused on aging, cognition and neurodegenerative and hippocampal-related neurological diseases mentioned above. In the second section, we reviewed the therapeutic approaches, particularly gene therapy, using glial cell-line-derived neurotrophic factor or its gene, as a key molecule in the development of neurological disorders. In the third section, we pointed at the potential of regenerative medicine, as an emerging and less explored strategy for the treatment of hippocampal disorders. We briefly reviewed the use of partial reprogramming to restore brain functions, non-neuronal cell reprogramming to generate neural stem cells, and neural progenitor cells as source-specific neuronal types to be implanted in animal models of specific neurodegenerative disorders.
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Affiliation(s)
- Priscila Chiavellini
- Biochemistry Research Institute of La Plata (INIBIOLP)-Histology and Embryology B, School of Medical Sciences, National University of La Plata (UNLP), La Plata, Buenos Aires, Argentina
| | - Martina Canatelli-Mallat
- Biochemistry Research Institute of La Plata (INIBIOLP)-Histology and Embryology B, School of Medical Sciences, National University of La Plata (UNLP), La Plata, Buenos Aires, Argentina
| | - Marianne Lehmann
- Biochemistry Research Institute of La Plata (INIBIOLP)-Histology and Embryology B, School of Medical Sciences, National University of La Plata (UNLP), La Plata, Buenos Aires, Argentina
| | - Rodolfo G Goya
- Biochemistry Research Institute of La Plata (INIBIOLP)-Histology and Embryology B, School of Medical Sciences, National University of La Plata (UNLP), La Plata, Buenos Aires, Argentina
| | - Gustavo R Morel
- Biochemistry Research Institute of La Plata (INIBIOLP)-Histology and Embryology B, School of Medical Sciences, National University of La Plata (UNLP), La Plata, Buenos Aires, Argentina
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14
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Early Development of the GABAergic System and the Associated Risks of Neonatal Anesthesia. Int J Mol Sci 2021; 22:ijms222312951. [PMID: 34884752 PMCID: PMC8657958 DOI: 10.3390/ijms222312951] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 11/19/2021] [Accepted: 11/25/2021] [Indexed: 12/30/2022] Open
Abstract
Human and animal studies have elucidated the apparent neurodevelopmental effects resulting from neonatal anesthesia. Observations of learning and behavioral deficits in children, who were exposed to anesthesia early in development, have instigated a flurry of studies that have predominantly utilized animal models to further interrogate the mechanisms of neonatal anesthesia-induced neurotoxicity. Specifically, while neonatal anesthesia has demonstrated its propensity to affect multiple cell types in the brain, it has shown to have a particularly detrimental effect on the gamma aminobutyric acid (GABA)ergic system, which contributes to the observed learning and behavioral deficits. The damage to GABAergic neurons, resulting from neonatal anesthesia, seems to involve structure-specific changes in excitatory-inhibitory balance and neurovascular coupling, which manifest following a significant interval after neonatal anesthesia exposure. Thus, to better understand how neonatal anesthesia affects the GABAergic system, we first review the early development of the GABAergic system in various structures that have been the focus of neonatal anesthesia research. This is followed by an explanation that, due to the prolonged developmental curve of the GABAergic system, the entirety of the negative effects of neonatal anesthesia on learning and behavior in children are not immediately evident, but instead take a substantial amount of time (years) to fully develop. In order to address these concerns going forward, we subsequently offer a variety of in vivo methods which can be used to record these delayed effects.
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15
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Proença ICT, Gonçalves LK, Schmitz F, Mello A, Funchal CS, Wyse A, Dani C. Purple grape juice consumption during the gestation reduces acetylcholinesterase activity and oxidative stress levels provoked by high-fat diet in hippocampus from adult female rats descendants. AN ACAD BRAS CIENC 2021; 93:e20191002. [PMID: 34190844 DOI: 10.1590/0001-3765202120191002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 01/27/2020] [Indexed: 01/03/2023] Open
Abstract
The enzyme acetylcholinesterase participates in the end of cholinergic transmission and it has been shown that its activity is increased in some diseases that affect the brain, including Alzheimer disease. The objective of this study was to investigate the effect of purple grape juice consumption with or without high-fat diet in the gestational and lactation period on acetylcholinesterase activity and oxidative stress parameters in the hippocampus of female descendants. During pregnancy and lactation, 40 female Wistar rats received a control diet or a high-fat diet, with half of them receiving grape juice. After lactation, the female descendants received water and control diet in ad libitum until euthanasia on the 120 postnatal day. Hippocampus from were removed for analysis of AChE activity, protein oxidation and lipid peroxidation. It was observed that high-fat diet consumption during the pregnancy increased the AChE activity and the grape juice reduced this activity in descendants. The same was observed in protein oxidation, the descendants from high-fat diet had significantly highest values, and grape juice decreased the levels. We conclude that dietary choices during pregnancy can alter the acetylcholinesterase levels and grape juice is an important alternative to improve this function in adulthood.
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Affiliation(s)
- Isabel C T Proença
- Programa de Pós-Graduação em Biociências e Reabilitação- Centro Universitário Metodista - IPA, Cel. Joaquim Pedro Salgado, 80, Rio Branco, 90420-060 Porto Alegre, RS, Brazil
| | - Luciana K Gonçalves
- Programa de Pós-Graduação em Biociências e Reabilitação- Centro Universitário Metodista - IPA, Cel. Joaquim Pedro Salgado, 80, Rio Branco, 90420-060 Porto Alegre, RS, Brazil
| | - Felipe Schmitz
- Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, Santa Cecília, 90035-003 Porto Alegre, RS, Brazil
| | - Alexandre Mello
- Programa de Pós-Graduação em Biociências e Reabilitação- Centro Universitário Metodista - IPA, Cel. Joaquim Pedro Salgado, 80, Rio Branco, 90420-060 Porto Alegre, RS, Brazil
| | - Claudia S Funchal
- Programa de Pós-Graduação em Biociências e Reabilitação- Centro Universitário Metodista - IPA, Cel. Joaquim Pedro Salgado, 80, Rio Branco, 90420-060 Porto Alegre, RS, Brazil
| | - Angela Wyse
- Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, Santa Cecília, 90035-003 Porto Alegre, RS, Brazil
| | - Caroline Dani
- Programa de Pós-Graduação em Biociências e Reabilitação- Centro Universitário Metodista - IPA, Cel. Joaquim Pedro Salgado, 80, Rio Branco, 90420-060 Porto Alegre, RS, Brazil.,Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, Centro Histórico, 90050-170 Porto Alegre, RS, Brazil
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16
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Lods M, Pacary E, Mazier W, Farrugia F, Mortessagne P, Masachs N, Charrier V, Massa F, Cota D, Ferreira G, Abrous DN, Tronel S. Adult-born neurons immature during learning are necessary for remote memory reconsolidation in rats. Nat Commun 2021; 12:1778. [PMID: 33741954 PMCID: PMC7979763 DOI: 10.1038/s41467-021-22069-4] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Accepted: 02/25/2021] [Indexed: 01/09/2023] Open
Abstract
Memory reconsolidation, the process by which memories are again stabilized after being reactivated, has strengthened the idea that memory stabilization is a highly plastic process. To date, the molecular and cellular bases of reconsolidation have been extensively investigated particularly within the hippocampus. However, the role of adult neurogenesis in memory reconsolidation is unclear. Here, we combined functional imaging, retroviral and chemogenetic approaches in rats to tag and manipulate different populations of rat adult-born neurons. We find that both mature and immature adult-born neurons are activated by remote memory retrieval. However, only specific silencing of the adult-born neurons immature during learning impairs remote memory retrieval-induced reconsolidation. Hence, our findings show that adult-born neurons immature during learning are required for the maintenance and update of remote memory reconsolidation.
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Affiliation(s)
- Marie Lods
- University of Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France
| | - Emilie Pacary
- University of Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France
| | - Wilfrid Mazier
- University of Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France
| | - Fanny Farrugia
- University of Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France
| | - Pierre Mortessagne
- University of Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France
| | - Nuria Masachs
- University of Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France
| | - Vanessa Charrier
- University of Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France
| | - Federico Massa
- University of Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France
| | - Daniela Cota
- University of Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France
| | - Guillaume Ferreira
- INRA, Bordeaux INP, Nutrition and Integrative Neurobiology, UMR 1286, Bordeaux Cedex, France
| | - Djoher Nora Abrous
- University of Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France.
| | - Sophie Tronel
- University of Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France.
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17
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Inhibition of mTOR signaling by genetic removal of p70 S6 kinase 1 increases anxiety-like behavior in mice. Transl Psychiatry 2021; 11:165. [PMID: 33723223 PMCID: PMC7960700 DOI: 10.1038/s41398-020-01187-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 12/16/2020] [Accepted: 12/17/2020] [Indexed: 12/31/2022] Open
Abstract
The mechanistic target of rapamycin (mTOR) is a ubiquitously expressed kinase that acts through two complexes, mTORC1 and mTORC2, to regulate protein homeostasis, as well as long lasting forms of synaptic and behavioral plasticity. Alteration of the mTOR pathway is classically involved in neurodegenerative disorders, and it has been linked to dysregulation of cognitive functions and affective states. However, information concerning the specific involvement of the p70 S6 kinase 1 (S6K1), a downstream target of the mTORC1 pathway, in learning and memory processes and in the regulation of affective states remains scant. To fill this gap, we exposed adult male mice lacking S6K1 to a battery of behavioral tests aimed at measuring their learning and memory capabilities by evaluating reference memory and flexibility with the Morris water maze, and associative memory using the contextual fear conditioning task. We also studied their anxiety-like and depression-like behaviors by, respectively, performing elevated plus maze, open field, light-dark emergence tests, and sucrose preference and forced swim tests. We found that deleting S6K1 leads to a robust anxious phenotype concomitant with associative learning deficits; these symptoms are associated with a reduction of adult neurogenesis and neuronal atrophy in the hippocampus. Collectively, these results provide grounds for the understanding of anxiety reports after treatments with mTOR inhibitors and will be critical for developing novel compounds targeting anxiety.
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18
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Sun C, Fu J, Qu Z, Jia L, Li D, Zhen J, Wang W. Chronic Intermittent Hypobaric Hypoxia Restores Hippocampus Function and Rescues Cognitive Impairments in Chronic Epileptic Rats via Wnt/β-catenin Signaling. Front Mol Neurosci 2021; 13:617143. [PMID: 33584201 PMCID: PMC7874094 DOI: 10.3389/fnmol.2020.617143] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 12/22/2020] [Indexed: 01/05/2023] Open
Abstract
Epilepsy is a complex neurological disorder with frequent psychiatric, cognitive, and social comorbidities in addition to recurrent seizures. Cognitive impairment, one of the most common comorbidities, has severe adverse effects on quality of life. Chronic intermittent hypobaric hypoxia (CIHH) has demonstrated neuroprotective efficacy in several neurological disease models. In the present study, we examined the effects of CIHH on cognition and hippocampal function in chronic epileptic rats. CIHH treatment rescued deficits in spatial and object memory, hippocampal neurogenesis, and synaptic plasticity in pilocarpine-treated epileptic rats. The Wnt/β-catenin pathway has been implicated in neural stem cell proliferation and synapse development, and Wnt/β-catenin pathway inhibition effectively blocked the neurogenic effects of CIHH. Our findings indicate that CIHH rescues cognitive deficits in epileptic rats via Wnt/β-catenin pathway activation. This study establishes CIHH and Wnt/β-catenin pathway regulators as potential treatments for epilepsy- induced cognitive impairments.
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Affiliation(s)
- Can Sun
- Key Laboratory of Neurology of Hebei Province, Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.,Department of Neurology, Peking University Third Hospital, Beijing, China
| | - Jian Fu
- Department of Emergency Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zhenzhen Qu
- Key Laboratory of Neurology of Hebei Province, Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Lijing Jia
- Key Laboratory of Neurology of Hebei Province, Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Dongxiao Li
- Key Laboratory of Neurology of Hebei Province, Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Junli Zhen
- Key Laboratory of Neurology of Hebei Province, Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Weiping Wang
- Key Laboratory of Neurology of Hebei Province, Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
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19
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Kerloch T, Farrugia F, Bouit L, Maître M, Terral G, Koehl M, Mortessagne P, Heng JIT, Blanchard M, Doat H, Leste-Lasserre T, Goron A, Gonzales D, Perrais D, Guillemot F, Abrous DN, Pacary E. The atypical Rho GTPase Rnd2 is critical for dentate granule neuron development and anxiety-like behavior during adult but not neonatal neurogenesis. Mol Psychiatry 2021; 26:7280-7295. [PMID: 34561615 PMCID: PMC8872985 DOI: 10.1038/s41380-021-01301-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 09/06/2021] [Accepted: 09/08/2021] [Indexed: 02/08/2023]
Abstract
Despite the central role of Rho GTPases in neuronal development, their functions in adult hippocampal neurogenesis remain poorly explored. Here, by using a retrovirus-based loss-of-function approach in vivo, we show that the atypical Rho GTPase Rnd2 is crucial for survival, positioning, somatodendritic morphogenesis, and functional maturation of adult-born dentate granule neurons. Interestingly, most of these functions are specific to granule neurons generated during adulthood since the deletion of Rnd2 in neonatally-born granule neurons only affects dendritogenesis. In addition, suppression of Rnd2 in adult-born dentate granule neurons increases anxiety-like behavior whereas its deletion in pups has no such effect, a finding supporting the adult neurogenesis hypothesis of anxiety disorders. Thus, our results are in line with the view that adult neurogenesis is not a simple continuation of earlier processes from development, and establish a causal relationship between Rnd2 expression and anxiety.
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Affiliation(s)
- Thomas Kerloch
- grid.412041.20000 0001 2106 639XUniv. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300 Bordeaux, France
| | - Fanny Farrugia
- grid.412041.20000 0001 2106 639XUniv. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300 Bordeaux, France
| | - Lou Bouit
- grid.462202.00000 0004 0382 7329Univ. Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR 5297, F-33000 Bordeaux, France
| | - Marlène Maître
- grid.412041.20000 0001 2106 639XLaser microdissection Facility, Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300 Bordeaux, France
| | - Geoffrey Terral
- grid.412041.20000 0001 2106 639XUniv. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300 Bordeaux, France
| | - Muriel Koehl
- grid.412041.20000 0001 2106 639XUniv. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300 Bordeaux, France
| | - Pierre Mortessagne
- grid.412041.20000 0001 2106 639XUniv. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300 Bordeaux, France
| | - Julian Ik-Tsen Heng
- grid.1032.00000 0004 0375 4078Curtin Health Innovation Research Institute, Curtin University, 6102 Bentley, WA Australia
| | - Mylène Blanchard
- grid.412041.20000 0001 2106 639XUniv. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300 Bordeaux, France
| | - Hélène Doat
- grid.412041.20000 0001 2106 639XLaser microdissection Facility, Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300 Bordeaux, France ,grid.412041.20000 0001 2106 639XTranscriptome Facility, Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300 Bordeaux, France
| | - Thierry Leste-Lasserre
- grid.412041.20000 0001 2106 639XTranscriptome Facility, Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300 Bordeaux, France
| | - Adeline Goron
- grid.412041.20000 0001 2106 639XUniv. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300 Bordeaux, France
| | - Delphine Gonzales
- grid.412041.20000 0001 2106 639XGenotyping Facility, Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300 Bordeaux, France
| | - David Perrais
- grid.462202.00000 0004 0382 7329Univ. Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR 5297, F-33000 Bordeaux, France
| | - François Guillemot
- grid.451388.30000 0004 1795 1830The Francis Crick Institute, 1 Midland Road, London, NW1 1AT UK
| | - Djoher Nora Abrous
- grid.412041.20000 0001 2106 639XUniv. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300 Bordeaux, France
| | - Emilie Pacary
- Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300, Bordeaux, France.
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20
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Fernandes RM, Corrêa MG, Aragão WAB, Nascimento PC, Cartágenes SC, Rodrigues CA, Sarmiento LF, Monteiro MC, Maia CDSF, Crespo-López ME, Lima RR. Preclinical evidences of aluminum-induced neurotoxicity in hippocampus and pre-frontal cortex of rats exposed to low doses. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2020; 206:111139. [PMID: 32861963 DOI: 10.1016/j.ecoenv.2020.111139] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 08/02/2020] [Accepted: 08/04/2020] [Indexed: 06/11/2023]
Abstract
Aluminum (Al) is a neurotoxicant agent implicated in several behavioral, neuropathological and neurochemical changes associated with cognitive impairments. Nevertheless, mechanisms of damage and safety concentrations are still very discussed. Thus, the main purpose of this study was to investigate whether two aluminum low doses were able to produce deleterious effects on cognition of adult rats, including oxidative stress in hippocampus and prefrontal cortex, two important areas for cognition. For this, thirty adult Wistar rats were divided into three groups: Al1 (8.3 mg/kg/day), Al2 (32 mg/kg/day) and Control (Ultrapure Water), in which all three groups received their solutions containing or not AlCl3 by intragastric gavage for 60 days. After the experimental period, the short- and long-term memories were assessed by the object recognition test and step-down inhibitory avoidance. After euthanizing, prefrontal cortex and hippocampus samples were dissected for Al levels measurement and evaluation of oxidative biochemistry. Only Al2 increased Al levels in hippocampal parenchyma significantly; both concentrations did not impair short-term memory, while long-term memory was affected in Al1 and Al2. In addition, oxidative stress was observed in prefrontal and hippocampus in Al1 and Al2. Our results indicate that, in a translational perspective, humans are subjected to deleterious effects of Al over cognition even when exposed to low concentrations, by triggering oxidative stress and poor long-term memory performance.
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Affiliation(s)
- Rafael Monteiro Fernandes
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil
| | - Márcio Gonçalves Corrêa
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil
| | - Walessa Alana Bragança Aragão
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil
| | - Priscila Cunha Nascimento
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil
| | - Sabrina C Cartágenes
- Laboratory of Pharmacology of Inflammation and Behavior, Institute of Health Sciences, Federal University of Pará, Belém, PA, Brazil
| | - Caroline Azulay Rodrigues
- Laboratory of Microbiology and Immunology of Teaching and Research, Pharmacy Faculty, Institute of Health Science, Federal University of Pará, Belém, PA, Brazil
| | - Luis Felipe Sarmiento
- Laboratory of Neuroscience and Behavior, Federal University of Pará, Belém-Pará, Brazil
| | - Marta Chagas Monteiro
- Laboratory of Microbiology and Immunology of Teaching and Research, Pharmacy Faculty, Institute of Health Science, Federal University of Pará, Belém, PA, Brazil
| | - Cristiane do Socorro Ferraz Maia
- Laboratory of Pharmacology of Inflammation and Behavior, Institute of Health Sciences, Federal University of Pará, Belém, PA, Brazil
| | | | - Rafael Rodrigues Lima
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil.
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Fabricating an electroactive injectable hydrogel based on pluronic-chitosan/aniline-pentamer containing angiogenic factor for functional repair of the hippocampus ischemia rat model. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 117:111328. [DOI: 10.1016/j.msec.2020.111328] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Revised: 05/11/2020] [Accepted: 07/20/2020] [Indexed: 01/05/2023]
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Jurkowski MP, Bettio L, K. Woo E, Patten A, Yau SY, Gil-Mohapel J. Beyond the Hippocampus and the SVZ: Adult Neurogenesis Throughout the Brain. Front Cell Neurosci 2020; 14:576444. [PMID: 33132848 PMCID: PMC7550688 DOI: 10.3389/fncel.2020.576444] [Citation(s) in RCA: 120] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Accepted: 08/19/2020] [Indexed: 12/31/2022] Open
Abstract
Convincing evidence has repeatedly shown that new neurons are produced in the mammalian brain into adulthood. Adult neurogenesis has been best described in the hippocampus and the subventricular zone (SVZ), in which a series of distinct stages of neuronal development has been well characterized. However, more recently, new neurons have also been found in other brain regions of the adult mammalian brain, including the hypothalamus, striatum, substantia nigra, cortex, and amygdala. While some studies have suggested that these new neurons originate from endogenous stem cell pools located within these brain regions, others have shown the migration of neurons from the SVZ to these regions. Notably, it has been shown that the generation of new neurons in these brain regions is impacted by neurologic processes such as stroke/ischemia and neurodegenerative disorders. Furthermore, numerous factors such as neurotrophic support, pharmacologic interventions, environmental exposures, and stem cell therapy can modulate this endogenous process. While the presence and significance of adult neurogenesis in the human brain (and particularly outside of the classical neurogenic regions) is still an area of debate, this intrinsic neurogenic potential and its possible regulation through therapeutic measures present an exciting alternative for the treatment of several neurologic conditions. This review summarizes evidence in support of the classic and novel neurogenic zones present within the mammalian brain and discusses the functional significance of these new neurons as well as the factors that regulate their production. Finally, it also discusses the potential clinical applications of promoting neurogenesis outside of the classical neurogenic niches, particularly in the hypothalamus, cortex, striatum, substantia nigra, and amygdala.
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Affiliation(s)
- Michal P. Jurkowski
- Island Medical Program, University of British Columbia, Vancouver, BC, Canada
| | - Luis Bettio
- Division of Medical Sciences, University of Victoria, Victoria, BC, Canada
| | - Emma K. Woo
- Island Medical Program, University of British Columbia, Vancouver, BC, Canada
| | - Anna Patten
- Centre for Interprofessional Clinical Simulation Learning (CICSL), Royal Jubilee Hospital, Victoria, BC, Canada
| | - Suk-Yu Yau
- Department of Rehabilitation Sciences, Hong Kong Polytechnic University, Hung Hom, Hong Kong
| | - Joana Gil-Mohapel
- Island Medical Program, University of British Columbia, Vancouver, BC, Canada
- Division of Medical Sciences, University of Victoria, Victoria, BC, Canada
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Clé M, Eldin P, Briant L, Lannuzel A, Simonin Y, Van de Perre P, Cabié A, Salinas S. Neurocognitive impacts of arbovirus infections. J Neuroinflammation 2020; 17:233. [PMID: 32778106 PMCID: PMC7418199 DOI: 10.1186/s12974-020-01904-3] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Accepted: 07/17/2020] [Indexed: 12/15/2022] Open
Abstract
Arthropod-borne viruses or arbovirus, are most commonly associated with acute infections, resulting on various symptoms ranging from mild fever to more severe disorders such as hemorrhagic fever. Moreover, some arboviral infections can be associated with important neuroinflammation that can trigger neurological disorders including encephalitis, paralysis, ophthalmological impairments, or developmental defects, which in some cases, can lead to long-term defects of the central nervous system (CNS). This is well illustrated in Zika virus-associated congenital brain malformations but also in West Nile virus-induced synaptic dysfunctions that can last well beyond infection and lead to cognitive deficits. Here, we summarize clinical and mechanistic data reporting on cognitive disturbances triggered by arboviral infections, which may highlight growing public health issues spanning the five continents.
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Affiliation(s)
- Marion Clé
- Pathogenesis and Control of Chronic Infections, INSERM, University of Montpellier, Etablissement Français du Sang, Montpellier, France
| | - Patrick Eldin
- Institute of Research in Infectiology of Montpellier, CNRS, University of Montpellier, Montpellier, France
| | - Laurence Briant
- Institute of Research in Infectiology of Montpellier, CNRS, University of Montpellier, Montpellier, France
| | - Annie Lannuzel
- Neurology Unit, INSERM CIC 1424, Guadeloupe University Hospital, Université des Antilles, Pointe-à-Pitre, Guadeloupe, France
- INSERM U1127, CNRS, UMR7225, Brain and Spine Institute, Sorbonne University Medical School, Paris, France
| | - Yannick Simonin
- Pathogenesis and Control of Chronic Infections, INSERM, University of Montpellier, Etablissement Français du Sang, Montpellier, France
| | - Philippe Van de Perre
- Pathogenesis and Control of Chronic Infections, INSERM, University of Montpellier, Etablissement Français du Sang, CHU Montpellier, Montpellier, France
| | - André Cabié
- INSERM CIC 1424, Infectious Disease and Tropical Medicine Unit, Martinique University Hospital, Université des Antilles EA4537, Martinique, France.
| | - Sara Salinas
- Pathogenesis and Control of Chronic Infections, INSERM, University of Montpellier, Etablissement Français du Sang, Montpellier, France.
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Yoo DY, Cho SB, Jung HY, Kim W, Nam SM, Kim JW, Moon SM, Yoon YS, Kim DW, Choi SY, Hwang IK. Differential roles of exogenous protein disulfide isomerase A3 on proliferating cell and neuroblast numbers in the normal and ischemic gerbils. Brain Behav 2020; 10:e01534. [PMID: 31957985 PMCID: PMC7066343 DOI: 10.1002/brb3.1534] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 12/19/2019] [Accepted: 12/23/2019] [Indexed: 01/02/2023] Open
Abstract
INTRODUCTION We examined the effects of exogenous protein disulfide isomerase A3 (PDIA3) on hippocampal neurogenesis in gerbils under control and ischemic damage. METHODS To facilitate the delivery of PDIA3 to the brain, we constructed Tat-PDIA3 protein and administered vehicle (10% glycerol) or Tat-PDIA3 protein once a day for 28 days. On day 24 of vehicle or Tat-PDIA3 treatment, ischemia was transiently induced by occlusion of both common carotid arteries for 5 min. RESULTS Administration of Tat-PDIA3 significantly reduced ischemia-induced spontaneous motor activity, and the number of NeuN-positive nuclei in the Tat-PDIA3-treated ischemic group was significantly increased in the CA1 region compared to that in the vehicle-treated ischemic group. Ki67- and DCX-immunoreactive cells were significantly higher in the Tat-PDIA3-treated group compared to the vehicle-treated control group. In vehicle- and Tat-PDIA3-treated ischemic groups, the number of Ki67- and DCX-immunoreactive cells was significantly higher as compared to those in the vehicle- and Tat-PDIA3-treated control groups, respectively. In the dentate gyrus, the numbers of Ki67-immunoreactive cells were comparable between vehicle- and Tat-PDIA3-treated ischemic groups, while more DCX-immunoreactive cells were observed in the Tat-PDIA3-treated group. Transient forebrain ischemia increased the expression of phosphorylated cAMP-response element-binding protein (pCREB) in the dentate gyrus, but the administration of Tat-PDIA3 robustly increased pCREB-positive nuclei in the normal gerbils, but not in the ischemic gerbils. Brain-derived neurotrophic factor (BDNF) mRNA expression was significantly increased in the Tat-PDIA3-treated group compared to that in the vehicle-treated group. Transient forebrain ischemic increased BDNF mRNA levels in both vehicle- and Tat-PDIA3-treated groups, and there were no significant differences between groups. CONCLUSIONS These results suggest that Tat-PDIA3 enhances cell proliferation and neuroblast numbers in the dentate gyrus in normal, but not in ischemic gerbils, by increasing BDNF mRNA and phosphorylation of pCREB.
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Affiliation(s)
- Dae Young Yoo
- Department of Anatomy and Cell BiologyCollege of Veterinary Medicine, and Research Institute for Veterinary ScienceSeoul National UniversitySeoulSouth Korea
- Department of AnatomyCollege of MedicineSoonchunhyang UniversityCheonanSouth Korea
| | - Su Bin Cho
- Department of Biomedical Sciences, and Research Institute for Bioscience and BiotechnologyHallym UniversityChuncheonSouth Korea
| | - Hyo Young Jung
- Department of Anatomy and Cell BiologyCollege of Veterinary Medicine, and Research Institute for Veterinary ScienceSeoul National UniversitySeoulSouth Korea
| | - Woosuk Kim
- Department of Anatomy and Cell BiologyCollege of Veterinary Medicine, and Research Institute for Veterinary ScienceSeoul National UniversitySeoulSouth Korea
| | - Sung Min Nam
- Department of AnatomyCollege of Veterinary MedicineKonkuk UniversitySeoulSouth Korea
| | - Jong Whi Kim
- Department of Anatomy and Cell BiologyCollege of Veterinary Medicine, and Research Institute for Veterinary ScienceSeoul National UniversitySeoulSouth Korea
| | - Seung Myung Moon
- Department of NeurosurgeryDongtan Sacred Heart HospitalCollege of MedicineHallym UniversityHwaseongSouth Korea
- Research Institute for Complementary & Alternative MedicineHallym UniversityChuncheonSouth Korea
| | - Yeo Sung Yoon
- Department of Anatomy and Cell BiologyCollege of Veterinary Medicine, and Research Institute for Veterinary ScienceSeoul National UniversitySeoulSouth Korea
| | - Dae Won Kim
- Department of Biochemistry and Molecular BiologyResearch Institute of Oral SciencesCollege of DentistryGangneung‐Wonju National UniversityGangneungSouth Korea
| | - Soo Young Choi
- Department of Biomedical Sciences, and Research Institute for Bioscience and BiotechnologyHallym UniversityChuncheonSouth Korea
| | - In Koo Hwang
- Department of Anatomy and Cell BiologyCollege of Veterinary Medicine, and Research Institute for Veterinary ScienceSeoul National UniversitySeoulSouth Korea
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Bekiari C, Grivas I, Tsingotjidou A, Papadopoulos GC. Adult neurogenesis and gliogenesis in the dorsal and ventral canine hippocampus. J Comp Neurol 2019; 528:1216-1230. [PMID: 31743444 DOI: 10.1002/cne.24818] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 11/08/2019] [Accepted: 11/08/2019] [Indexed: 12/13/2022]
Abstract
Dentate gyrus (DG) of the mammalian hippocampus gives rise to new neurons and astrocytes all through adulthood. Canine hippocampus presents many similarities in fetal development, anatomy, and physiology with human hippocampus, establishing canines as excellent animal models for the study of adult neurogenesis. In the present study, BrdU-dated cells of the structurally and functionally dissociated dorsal (dDG) and ventral (vDG) adult canine DG were comparatively examined over a period of 30 days. Each part's neurogenic potential, radial glia-like neural stem cells (NSCs) proliferation and differentiation, migration, and maturation of their progenies were evaluated at 2, 5, 14, and 30 days post BrdU administration, with the use of selected markers (glial fibrillary acidic protein, doublecortin, calretinin and calbindin). Co-staining of BrdU+ cells with NeuN or S100B permitted the parallel study of the ongoing neurogenesis and gliogenesis. Our findings reveal the comparatively higher populations of residing granule cells, proliferating NSCs and BrdU+ neurons in the dDG, whereas newborn neurons of the vDG showed a prolonged differentiation, migration, and maturation. Newborn astrocytes were found all along the dorso-ventral axis, counting however for only 11% of newborn cell population. Comparative evaluation of adult canine and rat neurogenesis revealed significant differences in the distribution of resident and newborn granule cells along the dorso-ventral axis, division pattern of adult NSCs, maturation time plan of newborn neurons, and ongoing gliogenesis. Concluding, spatial and temporal features of adult canine neurogenesis are similar to that of other gyrencephalic species, including humans, and justify the comparative examination of adult neurogenesis across mammalian species.
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Affiliation(s)
- Chryssa Bekiari
- Laboratory of Anatomy, Histology & Embryology, Faculty of Veterinary Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Ioannis Grivas
- Laboratory of Anatomy, Histology & Embryology, Faculty of Veterinary Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Anastasia Tsingotjidou
- Laboratory of Anatomy, Histology & Embryology, Faculty of Veterinary Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Georgios C Papadopoulos
- Laboratory of Anatomy, Histology & Embryology, Faculty of Veterinary Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
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van Dijk RM, Wiget F, Wolfer DP, Slomianka L, Amrein I. Consistent within-group covariance of septal and temporal hippocampal neurogenesis with behavioral phenotypes for exploration and memory retention across wild and laboratory small rodents. Behav Brain Res 2019; 372:112034. [DOI: 10.1016/j.bbr.2019.112034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 05/22/2019] [Accepted: 06/11/2019] [Indexed: 12/20/2022]
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Protective effects of melatonin against valproic acid-induced memory impairments and reductions in adult rat hippocampal neurogenesis. Neuroscience 2019; 406:580-593. [DOI: 10.1016/j.neuroscience.2019.02.022] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Revised: 02/13/2019] [Accepted: 02/14/2019] [Indexed: 01/12/2023]
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Abstract
Interest for the use of oxytocin as a treatment for addiction began over 40years ago. Better known for its roles in parturition, lactation and pair bonding, oxytocin also has anxiolytic properties, reduces immune and inflammatory responses, and has a role in learning and memory. In this chapter, oxytocin effects on addiction processes are described by highlighting research findings that have used oxytocin within current preclinical animal models of addiction, relapse, or craving. First, we provide a brief background of the endogenous oxytocin system followed by descriptions of the behavioral models used to study addiction, including models of drug taking and seeking. Then we review recent preclinical studies that have used oxytocin as a therapeutic intervention throughout multiple stages of the addiction cycle from a behavioral and neurobiological perspective. These models encompass the entire range of the addiction cycle including acquisition and maintenance of drug taking, withdrawal and craving during periods of drug abstinence, and ultimately relapse. We then posit several theories about how oxytocin interacts with both drug and social reward, as well as presenting a mechanistic account of how specific oxytocin receptor localization may contribute to oxytocin's efficacy as an addiction therapeutic.
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29
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Sarbu M, Vukelić Ž, Clemmer DE, Zamfir AD. Ion mobility mass spectrometry provides novel insights into the expression and structure of gangliosides in the normal adult human hippocampus. Analyst 2018; 143:5234-5246. [DOI: 10.1039/c8an01118d] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
General work-flow for ganglioside analysis by IM-MS.
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Affiliation(s)
- Mirela Sarbu
- National Institute for Research and Development in Electrochemistry and Condensed Matter
- Timisoara
- Romania
| | - Željka Vukelić
- Department of Chemistry and Biochemistry
- University of Zagreb Medical School
- Zagreb
- Croatia
| | | | - Alina D. Zamfir
- National Institute for Research and Development in Electrochemistry and Condensed Matter
- Timisoara
- Romania
- “Aurel Vlaicu” University of Arad
- Arad
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30
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Sherstnev VV, Kedrov AV, Solov’eva OA, Gruden’ MA, Konovalova EV, Kalinin IA, Proshin AT. The effects of α-synuclein oligomers on neurogenesis in the hippocampus and the behavior of aged mice. NEUROCHEM J+ 2017. [DOI: 10.1134/s1819712417040092] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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Kent BA, Mistlberger RE. Sleep and hippocampal neurogenesis: Implications for Alzheimer's disease. Front Neuroendocrinol 2017; 45:35-52. [PMID: 28249715 DOI: 10.1016/j.yfrne.2017.02.004] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Revised: 01/23/2017] [Accepted: 02/24/2017] [Indexed: 01/29/2023]
Abstract
Alzheimer's disease (AD) is the most common cause of dementia and currently there are no effective disease-modifying treatments available. Hallmark symptoms of AD include impaired hippocampus-dependent episodic memory and disrupted sleep and circadian rhythms. The pathways connecting these symptoms are of particular interest because it is well established that sleep and circadian disruption can impair hippocampus-dependent learning and memory. In rodents, these procedures also markedly suppress adult hippocampal neurogenesis, a form of brain plasticity that is believed to play an important role in pattern separation, and thus episodic memory. A causal role for sleep disruptions in AD pathophysiology is suggested by evidence for sleep-dependent glymphatic clearance of metabolic waste products from the brain. This review explores a complementary hypothesis that sleep and circadian disruptions in AD contribute to cognitive decline by activating neuroendocrine and neuroinflammatory signaling pathways that suppress hippocampal neurogenesis. Evidence for this hypothesis underscores the promise of sleep, circadian rhythms, and neurogenesis as therapeutic targets for remediation of memory impairment in AD.
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Affiliation(s)
- Brianne A Kent
- Division of Neurology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada
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Reichelt AC. Adolescent Maturational Transitions in the Prefrontal Cortex and Dopamine Signaling as a Risk Factor for the Development of Obesity and High Fat/High Sugar Diet Induced Cognitive Deficits. Front Behav Neurosci 2016; 10:189. [PMID: 27790098 PMCID: PMC5061823 DOI: 10.3389/fnbeh.2016.00189] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Accepted: 09/23/2016] [Indexed: 01/12/2023] Open
Abstract
Adolescence poses as both a transitional period in neurodevelopment and lifestyle practices. In particular, the developmental trajectory of the prefrontal cortex (PFC), a critical region for behavioral control and self-regulation, is enduring, not reaching functional maturity until the early 20 s in humans. Furthermore, the neurotransmitter dopamine is particularly abundant during adolescence, tuning the brain to rapidly learn about rewards and regulating aspects of neuroplasticity. Thus, adolescence is proposed to represent a period of vulnerability towards reward-driven behaviors such as the consumption of palatable high fat and high sugar diets. This is reflected in the increasing prevalence of obesity in children and adolescents as they are the greatest consumers of “junk foods”. Excessive consumption of diets laden in saturated fat and refined sugars not only leads to weight gain and the development of obesity, but experimental studies with rodents indicate they evoke cognitive deficits in learning and memory process by disrupting neuroplasticity and altering reward processing neurocircuitry. Consumption of these high fat and high sugar diets have been reported to have a particularly pronounced impact on cognition when consumed during adolescence, demonstrating a susceptibility of the adolescent brain to enduring cognitive deficits. The adolescent brain, with heightened reward sensitivity and diminished behavioral control compared to the mature adult brain, appears to be a risk for aberrant eating behaviors that may underpin the development of obesity. This review explores the neurodevelopmental changes in the PFC and mesocortical dopamine signaling that occur during adolescence, and how these potentially underpin the overconsumption of palatable food and development of obesogenic diet-induced cognitive deficits.
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Affiliation(s)
- Amy C Reichelt
- School of Health and Biomedical Sciences, RMIT University Melbourne, VIC, Australia
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Neuronal prolyl-4-hydroxylase 2 deficiency improves cognitive abilities in a murine model of cerebral hypoperfusion. Exp Neurol 2016; 286:93-106. [PMID: 27720797 DOI: 10.1016/j.expneurol.2016.10.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Revised: 09/14/2016] [Accepted: 10/04/2016] [Indexed: 12/29/2022]
Abstract
Episodes of cerebral hypoxia/ischemia increase the risk of dementia, which is associated with impaired learning and memory. Previous studies in rodent models of dementia indicated a favorable effect of the hypoxia-inducible factor (HIF) targets VEGF (vascular endothelial growth factor) and erythropoietin (Epo). In the present study we thus investigated whether activation of the entire adaptive HIF pathway in neurons by cell-specific deletion of the HIF suppressor prolyl-4-hydroxylase 2 (PHD2) improves cognitive abilities in young (3months) and old (18-28months) mice suffering from chronic brain hypoperfusion. Mice underwent permanent occlusion of the left common carotid artery, and cognitive function was assessed using the Morris water navigation task. Under conditions of both normal and decreased brain perfusion, neuronal PHD2 deficiency resulted in improved and faster spatial learning in young mice, which was preserved to some extent also in old animals. The loss of PHD2 in neurons resulted in enhanced hippocampal mRNA and protein levels of Epo and VEGF, but did not alter local microvascular density, dendritic spine morphology, or expression of synaptic plasticity-related genes in the hippocampus. Instead, better cognitive function in PHD2 deficient animals was accompanied by an increased number of neuronal precursor cells along the subgranular zone of the dentate gyrus. Overall, our current pre-clinical findings indicate an important role for the endogenous oxygen sensing machinery, encompassing PHDs, HIFs and HIF target genes, for proper cognitive function. Thus, pharmacological compounds affecting the PHD-HIF axis might well be suited to treat cognitive dysfunction and neurodegenerative processes.
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Lupus brain fog: a biologic perspective on cognitive impairment, depression, and fatigue in systemic lupus erythematosus. Immunol Res 2016; 63:26-37. [PMID: 26481913 DOI: 10.1007/s12026-015-8716-3] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Cognitive disturbances, mood disorders and fatigue are common in SLE patients with substantial adverse effects on function and quality of life. Attribution of these clinical findings to immune-mediated disturbances associated with SLE remains difficult and has compromised research efforts in these areas. Improved understanding of the role of the immune system in neurologic processes essential for cognition including synaptic plasticity, long term potentiation and adult neurogenesis suggests multiple potential mechanisms for altered central nervous system function associated with a chronic inflammatory illness such as SLE. This review will focus on the biology of cognition and neuroinflammation in normal circumstances and potential biologic mechanisms for cognitive impairment, depression and fatigue attributable to SLE.
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Brus M, Trouillet AC, Hellier V, Bakker J. Estradiol-induced neurogenesis in the female accessory olfactory bulb is required for the learning of the male odor. J Neurochem 2016; 138:457-68. [PMID: 27216894 DOI: 10.1111/jnc.13677] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Revised: 04/20/2016] [Accepted: 05/12/2016] [Indexed: 01/05/2023]
Abstract
Odors processed by the main and accessory olfactory bulbs (MOB, AOB) are important for sexual behavior. Interestingly, both structures continue to receive new neurons during adulthood. A role for olfactory neurogenesis in sexual behavior in female mice has recently been shown and gonadal hormones such as estradiol can modulate adult neurogenesis. Therefore, we wanted to determine the role of estradiol in learning the odors of sexual partners and in the adult neurogenesis of female aromatase knockout mice (ArKO), unable to produce estradiol. Female wild-type (WT) and ArKO mice were exposed to male odors during 7 days, and olfactory preferences, cell proliferation, cell survival and functional involvement of newborn neurons were analyzed, using BrdU injections, in combination with a marker of cell activation (Zif268) and neuronal fate (doublecortin, NeuN). Behavioral tasks indicated that both WT and ArKO females were able to discriminate between the odors of two different males, but ArKO mice failed to learn the familiar male odor. Proliferation of newborn cells was reduced in ArKO mice only in the dentate gyrus of the hippocampus. Olfactory exposure decreased cell survival in the AOB in WT females, suggesting a role for estradiol in a structure involved in sexual behavior. Finally, newborn neurons do not seem to be functionally involved in the AOB of ArKO mice compared with WT, when females were exposed to the odor of a familiar male, suggesting that estradiol-induced neurogenesis in the AOB is required for the learning of the male odor in female mice. Aromatase knockout mice (ArKO) presented deficits in olfactory preferences without affecting their olfactory discrimination abilities, and showed no functional involvement of newborn neurons in the accessory olfactory bulb (AOB) in response to the odor of a familiar male. These results suggest that estradiol-induced neurogenesis in the female AOB is required for the learning of the male odor.
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Affiliation(s)
- Maïna Brus
- Laboratory of Neuroendocrinology, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA) Neurosciences, University of Liège, Liège, Belgium
| | - Anne-Charlotte Trouillet
- Laboratory of Neuroendocrinology, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA) Neurosciences, University of Liège, Liège, Belgium
| | - Vincent Hellier
- Laboratory of Neuroendocrinology, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA) Neurosciences, University of Liège, Liège, Belgium
| | - Julie Bakker
- Laboratory of Neuroendocrinology, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA) Neurosciences, University of Liège, Liège, Belgium
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36
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Adult neurogenesis and pattern separation in rodents: A critical evaluation of data, tasks and interpretation. ACTA ACUST UNITED AC 2016. [DOI: 10.1007/s11515-016-1406-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
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Oliveira da Cruz J, Robin L, Drago F, Marsicano G, Metna-Laurent M. Astroglial type-1 cannabinoid receptor (CB1): A new player in the tripartite synapse. Neuroscience 2016; 323:35-42. [DOI: 10.1016/j.neuroscience.2015.05.002] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2015] [Revised: 04/25/2015] [Accepted: 05/01/2015] [Indexed: 01/08/2023]
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38
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Exercise prevents high-fat diet-induced impairment of flexible memory expression in the water maze and modulates adult hippocampal neurogenesis in mice. Neurobiol Learn Mem 2016; 131:26-35. [DOI: 10.1016/j.nlm.2016.03.002] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2015] [Revised: 02/21/2016] [Accepted: 03/02/2016] [Indexed: 02/05/2023]
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Huang GH, Yang XT, Chen K, Xing J, Guo L, Zhu L, Li HJ, Li XC, Zhang SY, Feng DF. Porf-2 Inhibits Neural Stem Cell Proliferation Through Wnt/β-Catenin Pathway by Its GAP Domain. Front Cell Neurosci 2016; 10:85. [PMID: 27064446 PMCID: PMC4814557 DOI: 10.3389/fncel.2016.00085] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Accepted: 03/18/2016] [Indexed: 01/18/2023] Open
Abstract
Neural stem cell (NSC) proliferation and differentiation play a pivotal role in the development of brain, the plasticity of the brain network, and the repair for brain function in CNS diseases. The mechanisms regulating NSC behavior are not well elucidated. Previous studies showed porf-2 functions as a modulator in central nerve system development. We here show that porf-2, a conserved family of RhoGAPs, is highly and specifically expressed in NSCs. We also demonstrate that porf-2 inhibits the proliferation of NSCs in vivo and in vitro, but has no effect on NSC differentiation. We investigated which domain is required for the role of porf-2 on NSC proliferation. By using neurosphere formation and Edu assay we confirmed the GAP domain is necessary for its function. In addition, we surveyed a few classical pathways on NSC proliferation and found that porf-2 inhibits NSC proliferation by suppressing the β-catenin nuclear translocation. Taken together, we show for the first time that porf-2 inhibits NSC proliferation through Wnt/β-catenin pathway by its GAP domain.
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Affiliation(s)
- Guo-Hui Huang
- Department of Neurosurgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China
| | - Xi-Tao Yang
- Department of Neurosurgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China
| | - Kui Chen
- Department of Neurosurgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China
| | - Jin Xing
- Department of Neurosurgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China
| | - Lin Guo
- Neuroscience Division, Department of Anatomy, Histology, and Embryology, Shanghai Jiao Tong University School of Medicine Shanghai, China
| | - Liang Zhu
- Department of Neurosurgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China
| | - Hong-Jiang Li
- Department of Neurosurgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China
| | - Xin-Cai Li
- Department of Neurosurgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China
| | - Sheng-Yi Zhang
- Department of Neurosurgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China
| | - Dong-Fu Feng
- Department of Neurosurgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineShanghai, China; Institute of Traumatic Medicine, Shanghai Jiao Tong University School of MedicineShanghai, China
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40
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Sadeghi A, Hami J, Razavi S, Esfandiary E, Hejazi Z. The Effect of Diabetes Mellitus on Apoptosis in Hippocampus: Cellular and Molecular Aspects. Int J Prev Med 2016; 7:57. [PMID: 27076895 PMCID: PMC4809120 DOI: 10.4103/2008-7802.178531] [Citation(s) in RCA: 87] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Accepted: 10/17/2015] [Indexed: 02/06/2023] Open
Abstract
Background: Diabetes mellitus is associated with cognitive deficits in humans and animals. These deficits are paralleled by neurophysiological and structural changes in brain. In diabetic animals, impairments of spatial learning, memory, and cognition occur in association with distinct changes in hippocampus, a key brain area for many forms of learning and memory and are particularly sensitive to changes in glucose homeostasis. However, the multifactorial pathogenesis of diabetic encephalopathy is not yet completely understood. Apoptosis plays a crucial role in diabetes-induce neuronal loss in hippocampus. Methods: The effects of diabetes on hippocampus and cognitive/behavioral dysfunctions in experimental models of diabetes are reviewed, with a focus on the negative impact on increased neuronal apoptosis and related cellular and molecular mechanisms. Results: Of all articles that were assessed, most of the experimental studies clearly showed that diabetes causes neuronal apoptosis in hippocampus through multiple mechanisms, including oxidative stress, inhibition of caspases, disturbance in expression of apoptosis regulator genes, as well as deficits in mitochondrial function. The balance between pro-apoptotic and anti-apoptotic signaling may determine the neuronal apoptotic outcome in vitro and in vivo models of experimental diabetes. Conclusions: Dissecting out the mechanisms responsible for diabetes-related changes in the hippocampal cell apoptosis helps improve treatment of impaired cognitive and memory functions in diabetic individuals.
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Affiliation(s)
- Akram Sadeghi
- Department of Anatomical Sciences and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Javad Hami
- Department of Anatomical Sciences, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Shahnaz Razavi
- Department of Anatomical Sciences and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ebrahim Esfandiary
- Department of Anatomical Sciences and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zahra Hejazi
- Department of Genetic Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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Hu P, Wang Y, Liu J, Meng FT, Qi XR, Chen L, van Dam AM, Joëls M, Lucassen PJ, Zhou JN. Chronic retinoic acid treatment suppresses adult hippocampal neurogenesis, in close correlation with depressive-like behavior. Hippocampus 2016; 26:911-23. [PMID: 26860546 DOI: 10.1002/hipo.22574] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/04/2016] [Indexed: 12/18/2022]
Abstract
Clinical studies have highlighted an association between retinoid treatment and depressive symptoms. As we had shown before that chronic application of all-trans retinoic acid (RA) potently activated the hypothalamus-pituitary-adrenal (HPA) stress axis, we here questioned whether RA also induced changes in adult hippocampal neurogenesis, a form of structural plasticity sensitive to stress and implicated in aspects of depression and hippocampal function. RA was applied intracerebroventricularly (i.c.v.) to adult rats for 19 days after which animals were subjected to tests for depressive-like behavior (sucrose preference) and spatial learning and memory (water maze) performance. On day 27, adult hippocampal neurogenesis and astrogliosis was quantified using BrdU (newborn cell survival), PCNA (proliferation), doublecortin (DCX; neuronal differentiation), and GFAP (astrocytes) as markers. RA was found to increase retinoic acid receptor-α (RAR-α) protein expression in the hippocampus, suggesting an activation of RA-induced signaling mechanisms. RA further potently suppressed cell proliferation, newborn cell survival as well as neurogenesis, but not astrogliosis. These structural plasticity changes were significantly correlated with scores for anhedonia, a core symptom of depression, but not with water maze performance. Our results suggest that RA-induced impairments in hippocampal neurogenesis correlate with depression-like symptoms but not with spatial learning and memory in this design. Thus, manipulations aimed to enhance neurogenesis may help ameliorate emotional aspects of RA-associated mood disorders. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Pu Hu
- Department of Neurobiology and Biophysics, CAS Key Laboratory of Brain Function and Diseases, School of Life Science, University of Science and Technology of China, Hefei, Anhui, China
| | - Yu Wang
- Department of Neurobiology and Biophysics, CAS Key Laboratory of Brain Function and Diseases, School of Life Science, University of Science and Technology of China, Hefei, Anhui, China
| | - Ji Liu
- Department of Neurobiology and Biophysics, CAS Key Laboratory of Brain Function and Diseases, School of Life Science, University of Science and Technology of China, Hefei, Anhui, China
| | - Fan-Tao Meng
- Department of Neurobiology and Biophysics, CAS Key Laboratory of Brain Function and Diseases, School of Life Science, University of Science and Technology of China, Hefei, Anhui, China
| | - Xin-Rui Qi
- Department of Neurobiology and Biophysics, CAS Key Laboratory of Brain Function and Diseases, School of Life Science, University of Science and Technology of China, Hefei, Anhui, China
| | - Lin Chen
- Department of Neurobiology and Biophysics, CAS Key Laboratory of Brain Function and Diseases, School of Life Science, University of Science and Technology of China, Hefei, Anhui, China
| | - Anne-Marie van Dam
- Department of Anatomy & Neurosciences, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands
| | - Marian Joëls
- Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Paul J Lucassen
- Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands
| | - Jiang-Ning Zhou
- Department of Neurobiology and Biophysics, CAS Key Laboratory of Brain Function and Diseases, School of Life Science, University of Science and Technology of China, Hefei, Anhui, China
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Smith N, Miquel-Kergoat S, Thuret S. The impact of mastication on cognition: Evidence for intervention and the role of adult hippocampal neurogenesis. ACTA ACUST UNITED AC 2016. [DOI: 10.3233/nua-150054] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Natalie Smith
- Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, The James Black Centre, London, UK
| | | | - Sandrine Thuret
- Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, The James Black Centre, London, UK
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43
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Lazarov O, Hollands C. Hippocampal neurogenesis: Learning to remember. Prog Neurobiol 2016; 138-140:1-18. [PMID: 26855369 DOI: 10.1016/j.pneurobio.2015.12.006] [Citation(s) in RCA: 191] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2015] [Revised: 12/15/2015] [Accepted: 12/30/2015] [Indexed: 12/16/2022]
Abstract
Alzheimer's disease, the most prevalent form of dementia in the elderly, is characterized by progressive memory loss and cognitive dysfunction. It has become increasingly clear that while neuronal cell loss in the entorhinal cortex and hippocampus occurs in Alzheimer's disease, it is preceded by a long period of deficits in the connectivity of the hippocampal formation that contributes to the vulnerability of these circuits. Hippocampal neurogenesis plays a role in the maintenance and function of the dentate gyrus and hippocampal circuitry. This review will examine the evidence suggesting that hippocampal neurogenesis plays a role in cognitive function that is affected in Alzheimer's disease, will discuss the cognitive assessments used for the detection of Alzheimer's disease in humans and rodent models of familial Alzheimer's disease, and their value for unraveling the mechanism underlying the development of cognitive impairments and dementia.
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Affiliation(s)
- Orly Lazarov
- Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA.
| | - Carolyn Hollands
- Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA
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Gøtzsche CR, Woldbye DPD. The role of NPY in learning and memory. Neuropeptides 2016; 55:79-89. [PMID: 26454711 DOI: 10.1016/j.npep.2015.09.010] [Citation(s) in RCA: 117] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2015] [Revised: 09/29/2015] [Accepted: 09/29/2015] [Indexed: 01/07/2023]
Abstract
High levels of NPY expression in brain regions important for learning and memory together with its neuromodulatory and neurotrophic effects suggest a regulatory role for NPY in memory processes. Therefore it is not surprising that an increasing number of studies have provided evidence for NPY acting as a modulator of neuroplasticity, neurotransmission, and memory. Here these results are presented in relation to the types of memory affected by NPY and its receptors. NPY can exert both inhibitory and stimulatory effects on memory, depending on memory type and phase, dose applied, brain region, and NPY receptor subtypes. Thus NPY act as a resilience factor by impairing associative implicit memory after stressful and aversive events, as evident in models of fear conditioning, presumably via Y1 receptors in the amygdala and prefrontal cortex. In addition, NPY impairs acquisition but enhances consolidation and retention in models depending on spatial and discriminative types of associative explicit memory, presumably involving Y2 receptor-mediated regulations of hippocampal excitatory transmission. Moreover, spatial memory training leads to increased hippocampal NPY gene expression that together with Y1 receptor-mediated neurogenesis could constitute necessary steps in consolidation and long-term retention of spatial memory. Altogether, NPY-induced effects on learning and memory seem to be biphasic, anatomically and temporally differential, and in support of a modulatory role of NPY at keeping the system in balance. Obtaining further insight into memory-related effects of NPY could inspire the engineering of new therapeutics targeting diseases where impaired learning and memory are central elements.
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Affiliation(s)
- C R Gøtzsche
- Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark.
| | - D P D Woldbye
- Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark
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45
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Hammelman J, Lobo D, Levin M. Artificial Neural Networks as Models of Robustness in Development and Regeneration: Stability of Memory During Morphological Remodeling. ARTIFICIAL NEURAL NETWORK MODELLING 2016. [DOI: 10.1007/978-3-319-28495-8_3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Impact of neonatal anoxia on adult rat hippocampal volume, neurogenesis and behavior. Behav Brain Res 2016; 296:331-338. [DOI: 10.1016/j.bbr.2015.08.039] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Revised: 08/26/2015] [Accepted: 08/30/2015] [Indexed: 01/02/2023]
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Bayer R, Franke H, Ficker C, Richter M, Lessig R, Büttner A, Weber M. Alterations of neuronal precursor cells in stages of human adult neurogenesis in heroin addicts. Drug Alcohol Depend 2015; 156:139-149. [PMID: 26416695 DOI: 10.1016/j.drugalcdep.2015.09.005] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2015] [Revised: 08/31/2015] [Accepted: 09/04/2015] [Indexed: 11/29/2022]
Abstract
BACKGROUND Adult neurogenesis has been shown to occur throughout life and different brain pathologies were demonstrated to be associated with altered neurogenesis. Here, an impact of heroin addiction on neurogenesis in humans is hypothesised. METHODS Post mortem hippocampal specimens of drug addicts with known heroin abuse and a group of non-addictive control subjects were analysed, using antibodies indicating different stages of neurogenesis. The subgranular zone of the dentate gyrus was examined qualitatively and quantitatively. RESULTS The data indicate (i) a decreased number of neural precursor cells, (ii) accompanied by low rates of proliferation and (iii) a marked loss of dendritic trees in targeting cells in heroin fatalities. (iv) The age-dependent increase of differentiating cells in the healthy controls was not observed in the addicts. Additionally, double immunofluorescence labelling indicated the precursor nature of Musashi-1 positive cells in the human subgranular zone of the dentate gyrus. CONCLUSIONS Present data firstly demonstrate the influence of drug addiction with known heroin abuse on different developmental stages of progenitors in the dentate gyrus. The patterns of antibody staining suggest a distinct inhibition of neurogenesis at the stage of neural precursor cells and revealed morphological changes in targeting cells in cases of heroin addicts as compared to healthy controls. These alterations could be considerable for memory and cognitive deficits as well as addictive behaviour in chronic drug abusers and may give rise to specific pro-neurogenic therapies.
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Affiliation(s)
- Ronny Bayer
- Institute of Legal Medicine, University of Leipzig, D-04103 Leipzig, Germany
| | - Heike Franke
- Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, D-04107 Leipzig, Germany
| | - Christoph Ficker
- Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, D-04107 Leipzig, Germany
| | - Monique Richter
- Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, D-04107 Leipzig, Germany
| | - Rüdiger Lessig
- Institute of Legal Medicine, University of Halle-Wittenberg, D-06112 Halle (Saale), Germany
| | - Andreas Büttner
- Institute of Forensic Medicine, Rostock University Medical Centre, D-18055 Rostock, Germany
| | - Marco Weber
- Institute of Legal Medicine, University of Halle-Wittenberg, D-06112 Halle (Saale), Germany.
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Anacker C, Denny CA, Hen R. Regulation of hippocampal memory traces by neurogenesis. NEUROGENESIS 2015; 2:e1025180. [PMID: 27604158 PMCID: PMC4973587 DOI: 10.1080/23262133.2015.1025180] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Revised: 02/24/2015] [Accepted: 02/25/2015] [Indexed: 12/27/2022]
Abstract
The hippocampus has long been known as a brain structure fundamental for memory formation and retrieval. Recent technological advances of cellular tracing techniques and optogenetic manipulation strategies have allowed to unravel important aspects of the cellular origin of memory, and have started to shed new light on the neuronal networks involved in encoding, consolidation and retrieval of memory in the hippocampus. In particular, memory traces, or engrams, that are formed during encoding in the dentate gyrus and CA3 region are crucial for memory retrieval and amenable to modulation by neuroplastic mechanisms, including adult hippocampal neurogenesis. Here, we will discuss how memory traces are being encoded at the cellular level, how they may contribute to pattern separation and pattern completion in the hippocampus, and how they can be associated with different experiences to express memories of opposite valence. We propose a mechanism by which adult hippocampal neurogenesis may contribute to the formation of engrams, which may be relevant not only for the encoding of contextual information, but also for mood abnormalities, such as anxiety and depression.
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Affiliation(s)
- Christoph Anacker
- Department of Psychiatry; Columbia University; New York, NY USA; Division of Integrative Neuroscience, New York State Psychiatric Institute/Research Foundation for Mental Hygiene; Inc. ; New York, NY USA
| | - Christine Ann Denny
- Department of Psychiatry; Columbia University; New York, NY USA; Division of Integrative Neuroscience, New York State Psychiatric Institute/Research Foundation for Mental Hygiene; Inc. ; New York, NY USA
| | - René Hen
- Department of Neuroscience; Columbia University; New York, NY USA; Department of Pharmacology; Columbia University; New York, NY USA; Department of Psychiatry; Columbia University; New York, NY USA; Division of Integrative Neuroscience; New York State Psychiatric Institute ; New York, NY USA
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Involvement of Adult Hippocampal Neurogenesis in Learning and Forgetting. Neural Plast 2015; 2015:717958. [PMID: 26380120 PMCID: PMC4561984 DOI: 10.1155/2015/717958] [Citation(s) in RCA: 106] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2014] [Revised: 03/12/2015] [Accepted: 03/31/2015] [Indexed: 12/20/2022] Open
Abstract
Adult hippocampal neurogenesis is a process involving the continuous generation of newborn neurons in the hippocampus of adult animals. Mounting evidence has suggested that hippocampal neurogenesis contributes to some forms of hippocampus-dependent learning and memory; however, the detailed mechanism concerning how this small number of newborn neurons could affect learning and memory remains unclear. In this review, we discuss the relationship between adult-born neurons and learning and memory, with a highlight on recently discovered potential roles of neurogenesis in pattern separation and forgetting.
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50
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Koehl M. Gene-environment interaction in programming hippocampal plasticity: focus on adult neurogenesis. Front Mol Neurosci 2015; 8:41. [PMID: 26300723 PMCID: PMC4523721 DOI: 10.3389/fnmol.2015.00041] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Accepted: 07/15/2015] [Indexed: 01/01/2023] Open
Abstract
Interactions between genes and environment are a critical feature of development and both contribute to shape individuality. They are at the core of vulnerability resiliency for mental illnesses. During the early postnatal period, several brain structures involved in cognitive and emotional processing, such as the hippocampus, still develop and it is likely that interferences with this neuronal development, which is genetically determined, might lead to long-lasting structural and functional consequences and increase the risk of developing psychopathology. One particular target is adult neurogenesis, which is involved in the regulation of cognitive and emotional processes. Insights into the dynamic interplay between genes and environmental factors in setting up individual rates of neurogenesis have come from laboratory studies exploring experience-dependent changes in adult neurogenesis as a function of individual’s genetic makeup. These studies have implications for our understanding of the mechanisms regulating adult neurogenesis, which could constitute a link between environmental challenges and psychopathology.
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Affiliation(s)
- Muriel Koehl
- INSERM U862, Magendie Neurocenter, Neurogenesis and Pathophysiology Group, Institut F. Magendie Bordeaux Cedex, France ; Université de Bordeaux Bordeaux, France
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