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Wang MN, Zuo GY, Wang X, Han Y, Xia CY, Pan CH, Guo YX, Wang YM, Yang H, Zhang WK, He J, Xu JK. Amelioration of gap junction dysfunction in a depression model by loganin: Involvement of GSK-3β/β-catenin signaling. JOURNAL OF ETHNOPHARMACOLOGY 2025; 341:119288. [PMID: 39732296 DOI: 10.1016/j.jep.2024.119288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 12/23/2024] [Accepted: 12/24/2024] [Indexed: 12/30/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Cornus officinalis Sieb. et Zucc has significant neuroprotective activity and has been widely studied for its potential to improve cognitive function. Our team's previous research has found that loganin isolated from Cornus officinalis has an antidepressant effect. Depression is a mental disorder accompanied by dysfunction of Connexin43 (Cx43)-formed astrocytic gap junctions. However, the precise mechanisms of loganin involved remain uncertain. AIM OF THE STUDY We aimed to examine the mechanism by which loganin produces its antidepressant properties. MATERIALS AND METHODS Using a chronic unpredictable stress (CUS) model of depression in rats, the study evaluated the behavioral responses to treatment with loganin, fluoxetine, and their combination. Biochemical analyses were conducted to measure the expression and phosphorylation status of Cx43, β-catenin, GSK-3β in the brain. In vitro experiments were also performed how loganin protects the gap junctions in astrocytes that have been exposed to corticosterone. RESULTS After four weeks of loganin treatment, rats exposed to CUS showed a decrease in depressive-like behaviors. When combined with fluoxetine, the antidepressant-like effects were observed faster than with either treatment alone. Loganin significantly increased Cx43 expression in the prefrontal cortex and ventral hippocampus, reversed Cx43 mimetic peptide Gap26-induced depressive-like behaviors, decreased Cx43 phosphorylation at Ser368, increased β-catenin levels, and promoted GSK-3β phosphorylation at Ser9. In vitro, loganin prevented corticosterone-induced damage to gap junctions between astrocytes, an effect that was negated by XAV-939 (β-catenin inhibitor). CONCLUSION These results implied that loganin could exert antidepressant-like effects by improving the gap junctions of astrocytes in the prefrontal cortex and hippocampus, acting through the GSK-3β/β-catenin signaling pathway. The combination of loganin with fluoxetine may provide a faster onset of antidepressant action compared to either treatment alone, highlighting the potential of loganin as a natural adjunct therapy for depression.
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Affiliation(s)
- Man-Ni Wang
- School of Life Sciences & School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China; Institute of Clinical Medical Sciences & Department of Pharmacy, China-Japan Friendship Hospital, Beijing, 100029, People's Republic of China
| | - Guo-Yan Zuo
- School of Life Sciences & School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China
| | - Xue Wang
- School of Life Sciences & School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China
| | - Yan Han
- School of Life Sciences & School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China
| | - Cong-Yuan Xia
- Institute of Clinical Medical Sciences & Department of Pharmacy, China-Japan Friendship Hospital, Beijing, 100029, People's Republic of China
| | - Chen-Hao Pan
- School of Life Sciences & School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China
| | - Yu-Xuan Guo
- School of Life Sciences & School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China
| | - Yu-Ming Wang
- School of Life Sciences & School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China
| | - Hua Yang
- School of Chemistry and Chemical Engineering, Shaanxi Key Laboratory of Chemical Reaction Engineering, Laboratory of New Energy & New Function Materials, Yan'an University, Yan'an, Shaanxi, 716000, People's Republic of China
| | - Wei-Ku Zhang
- Institute of Clinical Medical Sciences & Department of Pharmacy, China-Japan Friendship Hospital, Beijing, 100029, People's Republic of China.
| | - Jun He
- Institute of Clinical Medical Sciences & Department of Pharmacy, China-Japan Friendship Hospital, Beijing, 100029, People's Republic of China.
| | - Jie-Kun Xu
- School of Life Sciences & School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China.
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Bian Z, Li Z, Chang H, Luo J, Jian S, Zhang J, Lin P, Deng B, Deng J, Zhang L. Resveratrol Ameliorates Chronic Stress in Kennel Dogs and Mice by Regulating Gut Microbiome and Metabolome Related to Tryptophan Metabolism. Antioxidants (Basel) 2025; 14:195. [PMID: 40002382 PMCID: PMC11851397 DOI: 10.3390/antiox14020195] [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: 01/06/2025] [Revised: 01/29/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
Chronic stress poses threats to the physical and psychological well-being of dogs. Resveratrol (Res) is a polyphenol with antidepressant properties and has rarely been studied in dogs. This study aimed to investigate the stress-relieving effects and underlying mechanism of Res in dogs. Dogs were fed a basal diet supplemented with Res for 35 days. The fecal microbiota of the dogs was cultured with Res in vitro. The results show that Res improved the stress-related behaviors and increased the serum levels of 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), immunoglobulin A, and antioxidant capacity in dogs. Res downregulated the hormones of the hypothalamic-pituitary-adrenal axis. The abundance of butyric-producing bacteria, like Blautia, increased, while the growth of Fusobacterium related to gut inflammation was inhibited in the Res group. A higher content of fecal butyric acid was observed in the Res group. The metabolome indicated that Res increased the fecal and serum levels of tryptophan (Trp) and decreased the consumption of Trp by microorganisms. A chronic unpredictable mild stress mouse model was established, and Res was administered for 35 days. The results show that Res ameliorated the stress-related behavior and increased the levels of Trp and 5-HT in the whole brains of mice. The relative mRNA expression of genes associated with the tight junction protein, aryl hydrocarbon receptor, and Trp transporters in the colon were upregulated. In conclusion, Res could ameliorate canine stress by increasing 5-HT, BDNF, and the antioxidant capacity and improving the immune function and stress response, which was attributed to the role of Res in the restructuring of gut microbiota and the modulation of tryptophan metabolism.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Jinping Deng
- Laboratory of Companion Animal Science, Department of Animal Science, South China Agricultural University, Guangzhou 510642, China; (Z.B.); (Z.L.); (H.C.); (J.L.); (S.J.); (J.Z.); (P.L.); (B.D.)
| | - Lingna Zhang
- Laboratory of Companion Animal Science, Department of Animal Science, South China Agricultural University, Guangzhou 510642, China; (Z.B.); (Z.L.); (H.C.); (J.L.); (S.J.); (J.Z.); (P.L.); (B.D.)
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Li C, Ge H, Huang J, Si L, Sun L, Wu L, Xiao L, Xie Y, Wang G. Resveratrol alleviates depression-like behaviors by inhibiting ferroptosis via AKT/NRF2 pathway. Brain Res Bull 2025; 220:111136. [PMID: 39571625 DOI: 10.1016/j.brainresbull.2024.111136] [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: 09/09/2024] [Revised: 11/12/2024] [Accepted: 11/16/2024] [Indexed: 11/27/2024]
Abstract
Major depressive disorder (MDD) is common, and successful treatment remains challenging. Resveratrol, a naturally occurring polyphenol, has been shown to alleviate depression-like behaviors, but the underlying mechanisms remain unclear. We previously developed a new model of depression by inducing hippocampal ferroptosis in rats, suggesting that ferroptosis may be involved in the development of MDD. Here, we further explored the antidepressant-like effect of resveratrol and its association with ferroptosis. Male rats were exposed to chronic unpredictable mild stress (CUMS), with or without resveratrol, followed by comprehensive behavioral testing. In PC12 cells in vitro, LY294002 (an AKT inhibitor) and ML385 (an NRF2 inhibitor) were used to elucidate the involvement of AKT/NRF2 signaling in resveratrol-mediated ferroptosis. mRNA and protein levels of AKT/NRF2 pathway and ferroptosis-related targets were measured. Ferroptosis was quantified by measuring malondialdehyde (MDA), glutathione (GSH), and Fe2+ content and superoxide dismutase (SOD) activity. Resveratrol ameliorated depression-like behaviors in rats, simultaneously restoring AKT/NRF2 pathway and ferroptosis-related targets in the hippocampus downregulated by CUMS. Elevated markers of oxidative stress in plasma were attenuated by resveratrol. Furthermore, erastin induced ferroptosis and inhibited AKT/NRF2 signaling in PC12 cells, which was counteracted by resveratrol. Additionally, the impact of resveratrol on erastin-induced ferroptosis was reversed by LY294002 and ML385. This study demonstrates that resveratrol ameliorates depression-like behaviors by inhibiting ferroptosis via the AKT/NRF2 pathway.
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Affiliation(s)
- Chen Li
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
| | - Hailong Ge
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
| | - Junjie Huang
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
| | - Lujia Si
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
| | - Limin Sun
- Department of Psychiatry and Institute of Neuropsychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
| | - Lan Wu
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
| | - Ling Xiao
- Department of Psychiatry and Institute of Neuropsychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
| | - Yinping Xie
- Department of Psychiatry and Institute of Neuropsychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
| | - Gaohua Wang
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China; Department of Psychiatry and Institute of Neuropsychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
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Liu F, Jia Y, Zhao L, Xiao LN, Cheng X, Xiao Y, Zhang Y, Zhang Y, Yu H, Deng QE, Zhang Y, Feng Y, Wang J, Gao Y, Zhang X, Geng Y. Escin ameliorates CUMS-induced depressive-like behavior via BDNF/TrkB/CREB and TLR4/MyD88/NF-κB signaling pathways in rats. Eur J Pharmacol 2024; 984:177063. [PMID: 39426465 DOI: 10.1016/j.ejphar.2024.177063] [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: 06/24/2024] [Revised: 09/25/2024] [Accepted: 10/17/2024] [Indexed: 10/21/2024]
Abstract
Major depressive disorder (MDD) is a prevalent psychiatric disorder associated with brain inflammation and neuronal damage. Derived from the Aesculus chinensis Bunge fruit, escin has shown anti-inflammatory and neuroprotective effects. However, its potential as a treatment for MDD is unclear. This study investigates the antidepressant properties of escin using in vivo experimentation. The chronic unpredictable mild stress (CUMS) model was used to analyze the potential antidepressant effects and underlying mechanisms of escin. Wistar rats were exposed to CUMS for 35 consecutive days to induce MDD. The rats were then given either escin (1, 3, and 10 mg/kg) or fluoxetine (2 mg/kg) on a daily basis. Notably, escin significantly alleviated the depressive behaviors induced by CUMS, as evaluated through a series of behavioral assessments. Moreover, escin administration reduced TNF-α, IL-1β, and IL-6 levels in the hippocampus. It also decreased serum adrenal cortical hormone (ACTH) and corticosterone (CORT) levels while increasing 5-HT and Brain-derived neurotrophic factor (BDNF) levels in the CUMS rats, as measured by the enzyme-linked immunosorbent assay (ELISA). Pathological changes in the hippocampal regions were identified through Nissl staining, and Western blotting was used to quantify the protein levels of BDNF, TrkB, CREB, TLR4, MyD88, and NF-κB. Escin mitigated neuronal injury, elevated TrkB, BDNF, and CREB, and reduced TLR4, MyD88, and NF-κB protein levels in CUMS rats. The data from this study suggest that escin holds the potential for alleviating depression-like symptoms induced by CUMS. This effect may be mediated through the modulation of two signaling pathways, BDNF/TrkB/CREB and TLR4/MyD88/NF-κB.
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Affiliation(s)
- Fengjiao Liu
- Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; College of Integrative Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; Hebei International Cooperation Center for Ion Channel Function and Innovative Traditional Chinese Medicine, Shijiazhuang, Hebei, 050091, China
| | - Yaxin Jia
- Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; College of Integrative Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; Hebei International Cooperation Center for Ion Channel Function and Innovative Traditional Chinese Medicine, Shijiazhuang, Hebei, 050091, China
| | - Liwei Zhao
- Science and Technology Office, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China
| | - Li-Na Xiao
- Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; College of Integrative Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; Hebei International Cooperation Center for Ion Channel Function and Innovative Traditional Chinese Medicine, Shijiazhuang, Hebei, 050091, China
| | - Xizhen Cheng
- Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China
| | - Yingying Xiao
- Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; College of Integrative Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; Hebei International Cooperation Center for Ion Channel Function and Innovative Traditional Chinese Medicine, Shijiazhuang, Hebei, 050091, China
| | - Ying Zhang
- Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; College of Integrative Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; Hebei International Cooperation Center for Ion Channel Function and Innovative Traditional Chinese Medicine, Shijiazhuang, Hebei, 050091, China
| | - Yuling Zhang
- Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China
| | - Huimin Yu
- Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; College of Integrative Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; Hebei International Cooperation Center for Ion Channel Function and Innovative Traditional Chinese Medicine, Shijiazhuang, Hebei, 050091, China
| | - Qiao-En Deng
- The Eighth Hospital of Shijiazhuang, Shijiazhuang, Hebei, 050081, China
| | - Yuanyuan Zhang
- Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; Hebei International Cooperation Center for Ion Channel Function and Innovative Traditional Chinese Medicine, Shijiazhuang, Hebei, 050091, China
| | - Yimeng Feng
- College of Integrative Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China
| | - Junfang Wang
- College of Integrative Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China
| | - Yonggang Gao
- Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; Hebei International Cooperation Center for Ion Channel Function and Innovative Traditional Chinese Medicine, Shijiazhuang, Hebei, 050091, China; Department of Preventive Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang, Hebei, 050091, China.
| | - Xuan Zhang
- Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; Hebei International Cooperation Center for Ion Channel Function and Innovative Traditional Chinese Medicine, Shijiazhuang, Hebei, 050091, China; Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang, Hebei, 050091, China; Hebei Higher Education Institute Applied Technology Research Center on TCM Formula Preparation, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050091, China.
| | - Yunyun Geng
- Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; Hebei International Cooperation Center for Ion Channel Function and Innovative Traditional Chinese Medicine, Shijiazhuang, Hebei, 050091, China; Heibei Key Laboratory of Chinese Medicine Research on Cardiocerebrovascular Disease, Shijiazhuang, Hebei, 050091, China.
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He Y, Zhao Y, Lv RJ, Dong N, Wang X, Yu Q, Yue HM. Curcumin triggers the Wnt/β-catenin pathway and shields neurons from injury caused by intermittent hypoxia. Tissue Cell 2024; 91:102587. [PMID: 39454474 DOI: 10.1016/j.tice.2024.102587] [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: 05/10/2024] [Revised: 10/17/2024] [Accepted: 10/17/2024] [Indexed: 10/28/2024]
Abstract
The objective of this study was to explore the molecular basis through which Curcumin (Cur) mitigates neuronal damage caused by obstructive sleep apnea (OSA). HT22 was used to simulate intermittent hypoxia (IH) injury and explore the effect of Cur on these cells. We evaluated the cell viability, cytotoxicity, apoptosis, proliferation, and Wnt/β-catenin (WβC) pathway. IWR-1 was used to block the pathway and investigate the protective mechanism of Cur. We constructed an in vivo model of IH to validate the results of the cellular experiments. IH accelerated apoptosis and cytotoxicity, suppressed proliferation, and decreased the activity of the WβC pathway. Cur can significantly improve cell viability, reduce apoptosis rate and cell toxicity, promote cell proliferation, and up-regulate the WβC. After blocking the WβC pathway, the proliferative effect of Cur was observably weakened. In vivo, IH caused hippocampal damage and inhibited WβC pathway activity in mice, which was ameliorated by Cur treatment. This implies that Cur could be a novel treatment option for neurological impairment brought on by OSA.
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Affiliation(s)
- Yao He
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
| | - Yan Zhao
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
| | - Ren-Jun Lv
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
| | - Na Dong
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
| | - Xiao Wang
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
| | - Qin Yu
- The First Clinical Medical College, Lanzhou University, Lanzhou, China; Department of Respiratory and Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou, China
| | - Hong-Mei Yue
- The First Clinical Medical College, Lanzhou University, Lanzhou, China; Department of Respiratory and Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou, China.
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El-Kadi RA, AbdelKader NF, Zaki HF, Kamel AS. Vilazodone Alleviates Neurogenesis-Induced Anxiety in the Chronic Unpredictable Mild Stress Female Rat Model: Role of Wnt/β-Catenin Signaling. Mol Neurobiol 2024; 61:9060-9077. [PMID: 38584231 PMCID: PMC11496359 DOI: 10.1007/s12035-024-04142-3] [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] [Received: 08/10/2023] [Accepted: 03/19/2024] [Indexed: 04/09/2024]
Abstract
Defective β-catenin signaling is accompanied with compensatory neurogenesis process that may pave to anxiety. β-Catenin has a distinct role in alleviating anxiety in adolescence; however, it undergoes degradation by the degradation complex Axin and APC. Vilazodone (VZ) is a fast, effective antidepressant with SSRI activity and 5-HT1A partial agonism that amends somatic and/or psychic symptoms of anxiety. Yet, there is no data about anxiolytic effect of VZ on anxiety-related neurogenesis provoked by stress-reduced β-catenin signaling. Furthermore, females have specific susceptibility toward psychopathology. The aim of the present study is to uncover the molecular mechanism of VZ relative to Wnt/β-catenin signaling in female rats. Stress-induced anxiety was conducted by subjecting the rats to different stressful stimuli for 21 days. On the 15th day, stressed rats were treated with VZ(10 mg/kg, p.o.) alone or concomitant with the Wnt inhibitor: XAV939 (0.1 mg/kg, i.p.). Anxious rats showed low β-catenin level turned over by Axin-1 with unanticipated reduction of APC pursued with elevated protein levels of neurogenesis-stimulating proteins: c-Myc and pThr183-Erk likewise gene expressions of miR-17-5p and miR-18. Two weeks of VZ treatment showed anxiolytic effect figured by alleviation of hippocampal histological examination. VZ protected β-catenin signal via reduction in Axin-1 and elevation of APC conjugated with modulation of β-catenin downstream targets. The cytoplasmic β-catenin turnover by Axin-1 was restored by XAV939. Herein, VZ showed anti-anxiety effect, which may be in part through regaining the balance of the reduced β-catenin and its subsequent exaggerated response of p-Erk, c-Myc, Dicer-1, miR-17-5p, and miR-18.
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Affiliation(s)
- Rana A El-Kadi
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini, Cairo, 11562, Egypt
- Alexandria University Hospitals, Champollion Street, El-Khartoum Square, El Azareeta, Alexandria, 21131, Egypt
| | - Noha F AbdelKader
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini, Cairo, 11562, Egypt
| | - Hala F Zaki
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini, Cairo, 11562, Egypt
| | - Ahmed S Kamel
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini, Cairo, 11562, Egypt.
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Zaky DA, Mehny KA, Abdelrahman SS, El-Yamany MF, Kamel AS. Flibanserin conquers murine depressive pseudodementia by amending HPA axis, maladaptive inflammation and AKT/GSK/STAT/BDNF trajectory: Center-staging of the serotonergic/adrenergic circuitry. Eur J Pharmacol 2024; 980:176869. [PMID: 39117265 DOI: 10.1016/j.ejphar.2024.176869] [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: 03/06/2024] [Revised: 07/10/2024] [Accepted: 08/05/2024] [Indexed: 08/10/2024]
Abstract
Depressive pseudodementia (DPD) is a debilitating cognitive dysfunction that accompanies major and/or frequent depressive attacks. DPD has gained significant research attention owing to its negative effects on the patients' quality of life and productivity. This study tested the procognitive potential of Flibanserin (FBN), the serotonin (5HT) receptor modulator, against propranolol (PRP), as β/5HT1A receptors blocker. Serving this purpose, female Wistar Albino rats were subjected to chronic unpredictable stress (CUS) and subsequently treated with FBN only (3 mg/kg/day, p.o), PRP only (10 mg/kg/day, p.o), or PRP followed by FBN, using the same doses. FBN ameliorated the behavioral/cognitive alterations and calmed the hypothalamic-pituitary-adrenal (HPA) axis storm by reducing the levels of stress-related hormones, viz, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT) parallel to epinephrine (EPI) hyperstimulation. The maladaptive inflammatory response, comprising of interleukin (IL)-1β/6, and tumor necrosis factor (TNF)-α, was consequently blunted. This was contemporaneous to the partial restoration of the protein kinase-B (AKT)/glycogen synthase kinase (GSK)3β/signal transducer and activator of transcription (STAT)-3 survival trajectory and the reinstatement of the levels of brain derived neurotrophic factor (BDNF). Microscopically, FBN repaired the hippocampal architecture and lessened CD68/GFAP immunoreactivity. Pre-administration of PRP partially abolished FBN effect along the estimated parameters, except for 5HT2A receptor expression and epinephrine level, to prove 5HT1A receptor as a fulcrum initiator of the investigated pathway, while its sole administration worsened the underlying condition. Ultimately, these findings highlight the immense procognitive potential of FBN, offering a new paradigm for halting DPD advancement via synchronizing adrenergic/serotonergic circuitry.
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Affiliation(s)
- Doaa A Zaky
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo, 11562, Egypt.
| | | | - Sahar S Abdelrahman
- Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt
| | - Mohammed F El-Yamany
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo, 11562, Egypt
| | - Ahmed S Kamel
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo, 11562, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy and Drug Technology, Egyptian Chinese University, Cairo, Egypt
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Tseilikman VE, Tseilikman OB, Yegorov ON, Brichagina AA, Karpenko MN, Tseilikman DV, Shatilov VA, Zhukov MS, Novak J. Resveratrol: A Multifaceted Guardian against Anxiety and Stress Disorders-An Overview of Experimental Evidence. Nutrients 2024; 16:2856. [PMID: 39275174 PMCID: PMC11396965 DOI: 10.3390/nu16172856] [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] [Received: 07/15/2024] [Revised: 08/16/2024] [Accepted: 08/23/2024] [Indexed: 09/16/2024] Open
Abstract
The medicinal properties of resveratrol have garnered increasing attention from researchers. Extensive data have been accumulated on its use in treating cardiovascular diseases, immune system disorders, cancer, neurological diseases, and behavioral disorders. The protective mechanisms of resveratrol, particularly in anxiety-related stress disorders, have been well documented. However, less attention has been given to the side effects of resveratrol. This review explores not only the mechanisms underlying the anxiolytic effects of resveratrol but also the mechanisms that may lead to increased anxiety following resveratrol treatment. Understanding these mechanisms is crucial for enhancing the efficacy of resveratrol in managing anxiety disorders associated with stress and PTSD.
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Affiliation(s)
- Vadim E Tseilikman
- Scientific and Educational Center 'Biomedical Technologies', School of Medical Biology, South Ural State University, 454080 Chelyabinsk, Russia
- Zelman Institute of Medicine and Psychology, Novosibirsk State University, 630090 Novosibirsk, Russia
- Faculty of Fundamental Medicine, Chelyabinsk State University, 454001 Chelyabinsk, Russia
| | - Olga B Tseilikman
- Scientific and Educational Center 'Biomedical Technologies', School of Medical Biology, South Ural State University, 454080 Chelyabinsk, Russia
- Faculty of Fundamental Medicine, Chelyabinsk State University, 454001 Chelyabinsk, Russia
| | - Oleg N Yegorov
- Faculty of Fundamental Medicine, Chelyabinsk State University, 454001 Chelyabinsk, Russia
| | - Alina A Brichagina
- Faculty of Fundamental Medicine, Chelyabinsk State University, 454001 Chelyabinsk, Russia
| | - Marina N Karpenko
- Pavlov Department of Physiology, Institute of Experimental Medicine, 197376 Saint Petersburg, Russia
| | - David V Tseilikman
- Faculty of Fundamental Medicine, Chelyabinsk State University, 454001 Chelyabinsk, Russia
| | - Vladislav A Shatilov
- Scientific and Educational Center 'Biomedical Technologies', School of Medical Biology, South Ural State University, 454080 Chelyabinsk, Russia
- Faculty of Fundamental Medicine, Chelyabinsk State University, 454001 Chelyabinsk, Russia
| | - Maxim S Zhukov
- Faculty of Fundamental Medicine, Chelyabinsk State University, 454001 Chelyabinsk, Russia
| | - Jurica Novak
- Center for Artificial Intelligence and Cybersecurity, University of Rijeka, 51000 Rijeka, Croatia
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9
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Yang Y, Rao T, Wei S, Cheng J, Zhan Y, Lin T, Chen J, Zhong X, Jiang Y, Yang S. Role of inflammatory cytokines and the gut microbiome in vascular dementia: insights from Mendelian randomization analysis. Front Microbiol 2024; 15:1398618. [PMID: 39247699 PMCID: PMC11380139 DOI: 10.3389/fmicb.2024.1398618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Accepted: 07/10/2024] [Indexed: 09/10/2024] Open
Abstract
Background Both inflammatory cytokines and the gut microbiome are susceptibility factors for vascular dementia (VaD). The trends in the overall changes in the dynamics of inflammatory cytokines and in the composition of the gut microbiome are influenced by a variety of factors, making it difficult to fully explain the different effects of both on the different subtypes of VaD. Therefore, this Mendelian randomization (MR) study identified the inflammatory cytokines and gut microbiome members that influence the risk of developing VaD and their causal effects, and investigated whether inflammatory cytokines are gut microbiome mediators affecting VaD. Methods We obtained pooled genome-wide association study (GWAS) data for 196 gut microbiota and 41 inflammatory cytokines and used GWAS data for six VaD subtypes, namely, VaD (mixed), VaD (multiple infarctions), VaD (other), VaD (subcortical), VaD (sudden onset), and VaD (undefined). We used the inverse-variance weighted (IVW) method as the primary MR analysis method. We conducted sensitivity analyses and reverse MR analyses to examine reverse causal associations, enhancing the reliability and stability of the conclusions. Finally, we used multivariable MR (MVMR) analysis to assess the direct causal effects of inflammatory cytokines and the gut microbiome on the risk of VaD, and performed mediation MR analysis to explore whether inflammatory factors were potential mediators. Results Our two-sample MR study revealed relationships between the risk of six VaD subtypes and inflammatory cytokines and the gut microbiota: 7 inflammatory cytokines and 14 gut microbiota constituents were positively correlated with increased VaD subtype risk, while 2 inflammatory cytokines and 11 gut microbiota constituents were negatively correlated with decreased VaD subtype risk. After Bonferroni correction, interleukin-18 was correlated with an increased risk of VaD (multiple infarctions); macrophage migration inhibitory factor was correlated with an increased risk of VaD (sudden onset); interleukin-4 was correlated with a decreased risk of VaD (other); Ruminiclostridium 6 and Bacillales were positively and negatively correlated with the risk of VaD (undefined), respectively; Negativicutes and Selenomonadales were correlated with a decreased risk of VaD (mixed); and Melainabacteria was correlated with an increased risk of VaD (multiple infarctions). Sensitivity analyses revealed no multilevel effects or heterogeneity and no inverse causality between VaD and inflammatory cytokines or the gut microbiota. The MVMR results further confirmed that the causal effects of Negativicutes, Selenomonadales, and Melainabacteria on VaD remain significant. Mediation MR analysis showed that inflammatory cytokines were not potential mediators. Conclusion This study helps us to better understand the pathological mechanisms of VaD and suggests the potential value of targeting increases or decreases in inflammatory cytokines and gut microbiome members for VaD prevention and intervention.
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Affiliation(s)
- Yihan Yang
- The Institution of Rehabilitation Industry, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Ting Rao
- The Institution of Rehabilitation Industry, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Fujian Rehabilitation Hospital, Fujian University of Traditional Chinese Medicine Subsidiary Rehabilitation Hospital, Fuzhou, China
| | - Sheng Wei
- Department of General Practice, The Second Affiliated Hospital of Wannan Medical College, Anhui, China
| | - Jing Cheng
- Fujian Rehabilitation Hospital, Fujian University of Traditional Chinese Medicine Subsidiary Rehabilitation Hospital, Fuzhou, China
| | - Ying Zhan
- The Institution of Rehabilitation Industry, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Teng Lin
- The First Clinical Medical College, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Jincheng Chen
- The Institution of Rehabilitation Industry, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Fujian Rehabilitation Hospital, Fujian University of Traditional Chinese Medicine Subsidiary Rehabilitation Hospital, Fuzhou, China
| | - Xiaoling Zhong
- Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical School of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yijing Jiang
- Fujian Rehabilitation Hospital, Fujian University of Traditional Chinese Medicine Subsidiary Rehabilitation Hospital, Fuzhou, China
| | - Shanli Yang
- Fujian Rehabilitation Hospital, Fujian University of Traditional Chinese Medicine Subsidiary Rehabilitation Hospital, Fuzhou, China
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10
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Talaee N, Azadvar S, Khodadadi S, Abbasi N, Asli-Pashaki ZN, Mirabzadeh Y, Kholghi G, Akhondzadeh S, Vaseghi S. Comparing the effect of fluoxetine, escitalopram, and sertraline, on the level of BDNF and depression in preclinical and clinical studies: a systematic review. Eur J Clin Pharmacol 2024; 80:983-1016. [PMID: 38558317 DOI: 10.1007/s00228-024-03680-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 03/21/2024] [Indexed: 04/04/2024]
Abstract
Brain-derived neurotrophic factor (BDNF) dysfunction is one of the most important mechanisms underlying depression. It seems that selective serotonin reuptake inhibitors (SSRIs) improve depression via affecting BDNF level. In this systematic review, for the first time, we aimed to review the effect of three SSRIs including fluoxetine, escitalopram, and sertraline, on both depression and BDNF level in preclinical and clinical studies. PubMed electronic database was searched, and 193 articles were included in this study. After reviewing all manuscripts, only one important difference was found: subjects. We found that SSRIs induce different effects in animals vs. humans. Preclinical studies showed many controversial effects, while human studies showed only two effects: improvement of depression, with or without the improvement of BDNF. However, most studies used chronic SSRIs treatment, while acute SSRIs were not effectively used and evaluated. In conclusion, it seems that SSRIs are reliable antidepressants, and the improvement effect of SSRIs on depression is not dependent to BDNF level (at least in human studies).
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Affiliation(s)
- Nastaran Talaee
- Department of Psychology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Shataw Azadvar
- Department of Power Electronic, Faculty of Electrical Engineering, Sahand University of Technology, Tabriz, Iran
| | - Sanaz Khodadadi
- Student Research Committee, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Nahal Abbasi
- Department of Health Psychology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | | | - Yasaman Mirabzadeh
- Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran
| | - Gita Kholghi
- Department of Psychology, Faculty of Human Sciences, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran
| | - Shahin Akhondzadeh
- Psychiatric Research Center, Department of Psychiatry, Faculty of Medicine, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Salar Vaseghi
- Cognitive Neuroscience Lab, Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, 1419815477, Iran.
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11
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Xie Y, Wu Z, Qian Q, Yang H, Ma J, Luan W, Shang S, Li X. Apple polyphenol extract ameliorates sugary-diet-induced depression-like behaviors in male C57BL/6 mice by inhibiting the inflammation of the gut-brain axis. Food Funct 2024; 15:2939-2959. [PMID: 38406886 DOI: 10.1039/d3fo04606k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/27/2024]
Abstract
To explore whether apple polyphenol extract (APE) ameliorates sugary-diet-induced depression-like behaviors, thirty male C57BL/6 mice (3-4 weeks old) were assigned to three groups randomly to receive different treatments for 8 consecutive weeks: (1) control group (CON), (2) S-HSD group (60% high sucrose diet feeding with 0.1 mg mL-1 sucralose solution as drinking water), and (3) S-APE group (S-HSD feeding with 500 mg per (kg bw day) APE solution gavage). The S-HSD group showed significant depression-like behaviors compared with the CON group, which was manifested by an increased number of buried marbles in the marble burying test, prolonged immobility time in both the tail suspension test and forced swimming test, and cognitive impairment based on the Morris water maze test. However, APE intervention significantly improved the depression-like behaviors by reducing serum levels of corticosterone and adrenocorticotropic hormone, and increasing the serum level of IL-10. Moreover, APE intervention inhibited the activation of the NF-κB inflammatory pathway, elevated colonic MUC-2 protein expression, and elevated the colonic and hippocampal tight junction proteins of occludin and ZO-1. Furthermore, APE intervention increased the richness and diversity of gut microbiota by regulating the composition of microbiota, with increased relative abundance of Firmicutes and Bacteroidota, decreased relative abundance of Verrucomicrobiota at the phylum level, significantly lowered relative abundance of Akkermansia at the genus level, and rebalanced abnormal relative abundance of Muribaculaceae_unclassified, Coriobacteriaceae_UCG-002, and Lachnoclostridium induced by S-HSD feeding. Thus, our study supports the potential application of APE as a dietary intervention for ameliorating depression-like behavioral disorders.
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Affiliation(s)
- Yisha Xie
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215123, PR China.
| | - Zhengli Wu
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215123, PR China.
| | - Qingfan Qian
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215123, PR China.
| | - Hao Yang
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215123, PR China.
| | - Jieyu Ma
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215123, PR China.
| | - Wenxue Luan
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215123, PR China.
| | - Siyuan Shang
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215123, PR China.
| | - Xinli Li
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215123, PR China.
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu, PR China
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12
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Socała K, Żmudzka E, Lustyk K, Zagaja M, Brighenti V, Costa AM, Andres-Mach M, Pytka K, Martinelli I, Mandrioli J, Pellati F, Biagini G, Wlaź P. Therapeutic potential of stilbenes in neuropsychiatric and neurological disorders: A comprehensive review of preclinical and clinical evidence. Phytother Res 2024; 38:1400-1461. [PMID: 38232725 DOI: 10.1002/ptr.8101] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Revised: 12/01/2023] [Accepted: 12/12/2023] [Indexed: 01/19/2024]
Abstract
Neuropsychiatric disorders are anticipated to be a leading health concern in the near future, emphasizing an outstanding need for the development of new effective therapeutics to treat them. Stilbenes, with resveratrol attracting the most attention, are an example of multi-target compounds with promising therapeutic potential for a broad array of neuropsychiatric and neurological conditions. This review is a comprehensive summary of the current state of research on stilbenes in several neuropsychiatric and neurological disorders such as depression, anxiety, schizophrenia, autism spectrum disorders, epilepsy, traumatic brain injury, and neurodegenerative disorders. We describe and discuss the results of both in vitro and in vivo studies. The majority of studies concentrate on resveratrol, with limited findings exploring other stilbenes such as pterostilbene, piceatannol, polydatin, tetrahydroxystilbene glucoside, or synthetic resveratrol derivatives. Overall, although extensive preclinical studies show the potential benefits of stilbenes in various central nervous system disorders, clinical evidence on their therapeutic efficacy is largely missing.
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Affiliation(s)
- Katarzyna Socała
- Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Lublin, Poland
| | - Elżbieta Żmudzka
- Department of Social Pharmacy, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland
| | - Klaudia Lustyk
- Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland
| | - Mirosław Zagaja
- Department of Experimental Pharmacology, Institute of Rural Health, Lublin, Poland
| | - Virginia Brighenti
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Anna Maria Costa
- Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Marta Andres-Mach
- Department of Experimental Pharmacology, Institute of Rural Health, Lublin, Poland
| | - Karolina Pytka
- Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland
| | - Ilaria Martinelli
- Department of Neurosciences, Azienda Ospedaliero Universitaria di Modena, Modena, Italy
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
| | - Jessica Mandrioli
- Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
- Department of Neurosciences, Azienda Ospedaliero Universitaria di Modena, Modena, Italy
| | - Federica Pellati
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Giuseppe Biagini
- Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Piotr Wlaź
- Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Lublin, Poland
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El-Kadi RA, AbdelKader NF, Zaki HF, Kamel AS. Influence of β-catenin signaling on neurogenesis in neuropsychiatric disorders: Anxiety and depression. Drug Dev Res 2024; 85:e22157. [PMID: 38349261 DOI: 10.1002/ddr.22157] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 12/28/2023] [Accepted: 01/21/2024] [Indexed: 02/15/2024]
Abstract
It has been proven that stress, mainly in the early years of life, can lead to anxiety and mood problems. Current treatments for psychiatric disorders are not enough, and some of them show intolerable side effects, emphasizing the urgent need for new treatment targets. Hence, a better understanding of the different brain networks, which are involved in the response to anxiety and depression, may evoke treatments with more specific targets. One of these targets is β-catenin that regulates brain circuits. β-Catenin has a dual response toward stress, which may influence coping or vulnerability to stress response. Indeed, β-catenin signaling involves several processes such as inflammation-directed brain repair, inflammation-induced brain damage, and neurogenesis. Interestingly, β-catenin reduction is accompanied by low neurogenesis, which leads to anxiety and depression. However, in another state, this reduction activates a compensatory mechanism that enhances neurogenesis to protect against depression but may precipitate anxiety. Thus, understanding the molecular mechanism of β-catenin could enhance our knowledge about anxiety and depression's pathophysiology, potentially improving clinical results by targeting it. Herein, the different states of β-catenin were discussed, shedding light on possible drugs that showed action on psychiatric disorders through β-catenin.
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Affiliation(s)
| | - Noha F AbdelKader
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Hala F Zaki
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Ahmed S Kamel
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
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14
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Datseris I, Bouratzis N, Kotronis C, Datseris I, Tzanidaki ME, Rouvas A, Gouliopoulos N. One-year outcomes of resveratrol supplement with aflibercept versus aflibercept monotherapy in wet age-related macular degeneration. Int J Ophthalmol 2023; 16:1496-1502. [PMID: 37724273 PMCID: PMC10475632 DOI: 10.18240/ijo.2023.09.17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 07/17/2023] [Indexed: 09/20/2023] Open
Abstract
AIM To determine the one-year outcomes of resveratrol oral supplement in patients suffering from wet age-related macular degeneration (AMD). METHODS Fifty naïve and previously untreated patients suffering from wet AMD, were randomly assigned in two subgroups of 25 patients each. All the participants were treated with 3 monthly intravitreal injections of 2.0 mg aflibercept (IAIs) followed by injections "according to need", while in one group the patients also received daily two tablets of resveratrol oral supplement. Prior to treatment initiation, a complete ophthalmological examination, including best corrected visual acuity (BCVA) and contrast sensitivity evaluation, optical coherence tomography (OCT) scans, fundus autofluorescence (FAF), fluorescein angiography, indocyanine green angiography, and OCT angiography (OCTA), was performed to every participant, while all of them completed the Hospital Anxiety and Depression Scale (HADS) questionnaire, in order to assess their quality of life (QoL) status. The patients were assessed monthly for 1y with FAF, and OCT or OCTA; the main endpoints were the number IAIs, the changes in BCVA, in contrast sensitivity, and in patients' QoL status. RESULTS No significant differences were present between the groups regarding the baseline demographic and clinical data. Over the 12-month period, a similar number of IAIs was applied in both groups (4.52±1.00 vs 4.28±0.90, P=0.38), while the rest of the clinical data also did not differ significantly after the completion of the study period. However, for HADS Depression (11.88±2.51 vs 8.28±1.54, P<0.001) and HADS Anxiety (11.92±2.52 vs 7.76±1.51, P<0.001) questionnaires values, the score was significantly better in patients who received resveratrol supplements. Moreover, a statistically significant difference was detected in the mean change from baseline values of contrast sensitivity (0.17±0.19 vs 0.35±0.24, P=0.005), HADS Depression (0.08±1.38 vs -3.88±1.48, P<0.001), and HADS Anxiety (0.36±1.98 vs -5.12±2.70, P<0.001) scores, in favour of the patients treated with resveratrol supplements. CONCLUSION The resveratrol oral supplement is a complementary treatment in cases of wet AMD, highlighting its effectiveness in improving patients' QoL status.
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Affiliation(s)
| | - Nikolaos Bouratzis
- Specialized Eye Hospital “Ophthalmiatreion” Athinon, Athens 10672, Greece
| | - Charalambos Kotronis
- 2 Department of Ophthalmology, Medical School of University of Athens, “Attikon” University Hospital, Athens 12462, Greece
| | | | | | - Alexandros Rouvas
- 2 Department of Ophthalmology, Medical School of University of Athens, “Attikon” University Hospital, Athens 12462, Greece
| | - Nikolaos Gouliopoulos
- 2 Department of Ophthalmology, Medical School of University of Athens, “Attikon” University Hospital, Athens 12462, Greece
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15
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Tang HT, Zhang YP, Zhao S, Song C. Common mechanisms involved in lung cancer and depression: The dominant role of interleukin-6-IDO pathway in the lung-brain axis. JOURNAL OF AFFECTIVE DISORDERS REPORTS 2023. [DOI: 10.1016/j.jadr.2023.100580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/03/2023] Open
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16
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Puglisi-Allegra S, Lazzeri G, Busceti CL, Giorgi FS, Biagioni F, Fornai F. Lithium engages autophagy for neuroprotection and neuroplasticity: translational evidence for therapy. Neurosci Biobehav Rev 2023; 148:105148. [PMID: 36996994 DOI: 10.1016/j.neubiorev.2023.105148] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 03/23/2023] [Accepted: 03/26/2023] [Indexed: 03/30/2023]
Abstract
Here an overview is provided on therapeutic/neuroprotective effects of Lithium (Li+) in neurodegenerative and psychiatric disorders focusing on the conspicuous action of Li+ through autophagy. The effects on the autophagy machinery remain the key molecular mechanisms to explain the protective effects of Li+ for neurodegenerative diseases, offering potential therapeutic strategies for the treatment of neuropsychiatric disorders and emphasizes a crossroad linking autophagy, neurodegenerative disorders, and mood stabilization. Sensitization by psychostimulants points to several mechanisms involved in psychopathology, most also crucial in neurodegenerative disorders. Evidence shows the involvement of autophagy and metabotropic Glutamate receptors-5 (mGluR5) in neurodegeneration due to methamphetamine neurotoxicity as well as in neuroprotection, both in vitro and in vivo models. More recently, Li+ was shown to modulate autophagy through its action on mGluR5, thus pointing to an additional way of autophagy engagement by Li+ and to a substantial role of mGluR5 in neuroprotection related to neural e neuropsychiatry diseases. We propose Li+ engagement of autophagy through the canonical mechanisms of autophagy machinery and through the intermediary of mGluR5.
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17
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Therapeutic treatment with fluoxetine using the chronic unpredictable stress model induces changes in neurotransmitters and circulating miRNAs in extracellular vesicles. Heliyon 2023; 9:e13442. [PMID: 36852042 PMCID: PMC9958461 DOI: 10.1016/j.heliyon.2023.e13442] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 12/10/2022] [Accepted: 01/30/2023] [Indexed: 02/11/2023] Open
Abstract
The most widely prescribed antidepressant, fluoxetine (FLX), is known for its antioxidant and anti-inflammatory effects when administered post-stress. Few studies have evaluated the effects of FLX treatment when chronic stress has induced deleterious effects in patients. Our objective was to evaluate FLX treatment (20 mg/kg/day, i.v.) once these effects are manifested, and the drug's relation to extracellular circulating microRNAs associated with inflammation, a hedonic response (sucrose intake), the forced swim test (FST), and corticosterone levels (CORT) and monoamine concentrations in limbic areas. A group of Wistar rats was divided into groups: Control; FLX; CUMS (for six weeks of exposure to chronic, unpredictable mild stress); and CUMS + FLX, a mixed group. After CUMS, the rats performed the FST, and serum levels of CORT and six microRNAs (miR-16, -21, -144, -155, -146a, -223) were analyzed, as were levels of dopamine, noradrenaline, and serotonin in the prefrontal cortex, hippocampus, and hypothalamus. CUMS reduced body weight, sucrose intake, and hippocampal noradrenaline levels, but increased CORT, immobility behavior on the FST, dopamine concentrations in the prefrontal cortex, and all miRNAs except miR-146a expression. Administering FLX during CUMS reduced CORT levels and immobility behavior on the FST and increased the expression of miR-16, -21, -146a, -223, and dopamine. FLX protects against the deleterious effects of stress by reducing CORT and has an antidepressant effect on the FST, with minimally-modified neurotransmitter levels. FLX increased the expression of miRNAs as part of the antidepressant effect. It also regulates both neuroinflammation and serotoninergic neurotransmission through miRNAs, such as the miR-16.
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18
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Winiarska-Mieczan A, Kwiecień M, Jachimowicz-Rogowska K, Donaldson J, Tomaszewska E, Baranowska-Wójcik E. Anti-Inflammatory, Antioxidant, and Neuroprotective Effects of Polyphenols-Polyphenols as an Element of Diet Therapy in Depressive Disorders. Int J Mol Sci 2023; 24:ijms24032258. [PMID: 36768580 PMCID: PMC9916817 DOI: 10.3390/ijms24032258] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 01/15/2023] [Accepted: 01/20/2023] [Indexed: 01/26/2023] Open
Abstract
Depressive disorders can affect up to 350 million people worldwide, and in developed countries, the percentage of patients with depressive disorders may be as high as 10%. During depression, activation of pro-inflammatory pathways, mitochondrial dysfunction, increased markers of oxidative stress, and a reduction in the antioxidant effectiveness of the body are observed. It is estimated that approximately 30% of depressed patients do not respond to traditional pharmacological treatments. However, more and more attention is being paid to the influence of active ingredients in food on the course and risk of neurological disorders, including depression. The possibility of using foods containing polyphenols as an element of diet therapy in depression was analyzed in the review. The possibility of whether the consumption of products such as polyphenols could alleviate the course of depression or prevent the progression of it was also considered. Results from preclinical studies demonstrate the potential of phenolic compounds have the potential to reduce depressive behaviors by regulating factors related to oxidative stress, neuroinflammation, and modulation of the intestinal microbiota.
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Affiliation(s)
- Anna Winiarska-Mieczan
- Institute of Animal Nutrition and Bromatology, University of Life Sciences in Lublin, Akademicka St. 13, 20-950 Lublin, Poland
- Correspondence: ; Tel.: +48-81-445-67-44
| | - Małgorzata Kwiecień
- Institute of Animal Nutrition and Bromatology, University of Life Sciences in Lublin, Akademicka St. 13, 20-950 Lublin, Poland
| | - Karolina Jachimowicz-Rogowska
- Institute of Animal Nutrition and Bromatology, University of Life Sciences in Lublin, Akademicka St. 13, 20-950 Lublin, Poland
| | - Janine Donaldson
- School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa
| | - Ewa Tomaszewska
- Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Akademicka St. 12, 20-950 Lublin, Poland
| | - Ewa Baranowska-Wójcik
- Department of Biotechnology, Microbiology and Human Nutrition, University of Life Sciences in Lublin, Skromna St. 8, 20-704 Lublin, Poland
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Serafini G, Costanza A, Aguglia A, Amerio A, Trabucco A, Escelsior A, Sher L, Amore M. The Role of Inflammation in the Pathophysiology of Depression and Suicidal Behavior: Implications for Treatment. Med Clin North Am 2023; 107:1-29. [PMID: 36402492 DOI: 10.1016/j.mcna.2022.09.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Depression and suicidal behavior are 2 complex psychiatric conditions of significant public health concerns due to their debilitating nature. The need to enhance contemporary treatments and preventative approaches for these illnesses not only calls for distillation of current views on their pathogenesis but also provides an impetus for further elucidation of their novel etiological determinants. In this regard, inflammation has recently been recognized as a potentially important contributor to the development of depression and suicidal behavior. This review highlights key evidence that supports the presence of dysregulated neurometabolic and immunologic signaling and abnormal interaction with microbial species as putative etiological hallmarks of inflammation in depression as well as their contribution to the development of suicidal behavior. Furthermore, therapeutic insights addressing candidate mechanisms of pathological inflammation in these disorders are proposed.
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Affiliation(s)
- Gianluca Serafini
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health DINOGMI, Section of Psychiatry, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, Genoa 16132, Italy.
| | - Alessandra Costanza
- Department of Psychiatry, Faculty of Medicine, University of Geneva (UNIGE), Geneva, Switzerland, Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), Lugano, Switzerland; Department of Psychiatry, Faculty of Biomedical Sciences, University of Italian Switzerland (USI), Lugano, Switzerland
| | - Andrea Aguglia
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health DINOGMI, Section of Psychiatry, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, Genoa 16132, Italy
| | - Andrea Amerio
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health DINOGMI, Section of Psychiatry, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, Genoa 16132, Italy
| | - Alice Trabucco
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health DINOGMI, Section of Psychiatry, University of Genoa, Genoa, Italy
| | - Andrea Escelsior
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health DINOGMI, Section of Psychiatry, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, Genoa 16132, Italy
| | - Leo Sher
- James J. Peters VA Medical Center, Bronx, NY, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Psychiatry, New York, NY, USA
| | - Mario Amore
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health DINOGMI, Section of Psychiatry, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, Genoa 16132, Italy
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18β-Glycyrrhetinic Acid Ameliorates Neuroinflammation Linked Depressive Behavior Instigated by Chronic Unpredictable Mild Stress via Triggering BDNF/TrkB Signaling Pathway in Rats. Neurochem Res 2023; 48:551-569. [PMID: 36307572 PMCID: PMC9616426 DOI: 10.1007/s11064-022-03779-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 09/06/2022] [Accepted: 09/30/2022] [Indexed: 02/04/2023]
Abstract
Evidence shows that inflammatory responses may encompass the onset of severe depressive illness. Traditionally used licorice contains 18β-glycyrrhetinic acid (18βGA), which has been demonstrated to reduce inflammation and oxidative stress. This study investigates the antidepressant effects of 18βGA and the underlying mechanism in rats exposed to chronic unpredictable mild stress (CUMS). Wistar rats were exposed to CUMS for 36 consecutive days to establish depression. 18βGA (10, 20, and 50 mg/kg) or fluoxetine was given once daily (from day 30 to day 36). Thereafter, behavior parameters (sucrose preference test, forced-swimming test, open-field test, body weight), pro-inflammatory cytokines, neurotransmitters, adrenocorticotropic hormone (ACTH), corticosterone (CORT), and liver biomarkers were studied. Immunohistochemistry and western blot analyses were conducted to investigate the protein's expression. 18βGA (20 and 50 mg/kg) treatment increased sucrose intake, locomotion in the open-field test, decreased immobility time in the forced swim test, and improved body weight in CUMS-exposed rats. The therapy of 18βGA dramatically declined cytokines, ACTH and CORT and improved 5HT and norepinephrine in CUMS rats. Furthermore, BDNF and TrkB proteins were down-regulated in CUMS group, which was increased to varying degrees by 18βGA at doses of 20 and 50 mg/kg. Therefore, 18βGA ameliorates depressive-like behavior persuaded by chronic unpredictable mild stress, decreases neuroinflammation, liver biomarkers, stress hormones, and improves body weight, brain neurotransmitter concentration via activating on BDNF/TrkB signaling pathway in both PFC and hippocampus in rats.
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21
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Antidepressive Effect of Natural Products and Their Derivatives Targeting BDNF-TrkB in Gut-Brain Axis. Int J Mol Sci 2022; 23:ijms232314968. [PMID: 36499295 PMCID: PMC9737781 DOI: 10.3390/ijms232314968] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 11/24/2022] [Accepted: 11/25/2022] [Indexed: 12/04/2022] Open
Abstract
Modern neurological approaches enable detailed studies on the pathophysiology and treatment of depression. An imbalance in the microbiota-gut-brain axis contributes to the pathogenesis of depression. This extensive review aimed to elucidate the antidepressive effects of brain-derived neurotrophic factor (BDNF)-targeting therapeutic natural products and their derivatives on the gut-brain axis. This information could facilitate the development of novel antidepressant drugs. BDNF is crucial for neuronal genesis, growth, differentiation, survival, plasticity, and synaptic transmission. Signaling via BDNF and its receptor tropomyosin receptor kinase B (TrkB) plays a vital role in the etiopathogenesis of depression and the therapeutic mechanism of antidepressants. This comprehensive review provides information to researchers and scientists for the identification of novel therapeutic approaches for neuropsychiatric disorders, especially depression and stress. Future research should aim to determine the possible causative role of BDNF-TrkB in the gut-brain axis in depression, which will require further animal and clinical research as well as the development of analytical approaches.
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22
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Verma H, Shivavedi N, Tej GNVC, Kumar M, Nayak PK. Prophylactic administration of rosmarinic acid ameliorates depression-associated cardiac abnormalities in Wistar rats: Evidence of serotonergic, oxidative, and inflammatory pathways. J Biochem Mol Toxicol 2022; 36:e23160. [PMID: 35838106 DOI: 10.1002/jbt.23160] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 05/05/2022] [Accepted: 07/01/2022] [Indexed: 12/16/2022]
Abstract
Psychiatric disorders and associated cardiac comorbidities have increased the risk of mortality worldwide. Researchers reported that depression increases the possibility of future cardiac abnormalities by approximately 30%. Therefore, there is an unmet need to develop therapeutic interventions to treat depression and associated cardiac abnormalities. The present study was conducted to evaluate the prophylactic effect of rosmarinic acid (RA) against chronic unpredictable stress (CUS)-induced depression associated cardiac abnormalities in Wistar rats. The CUS paradigm, which comprised several stressors, was employed for 40 days to induce depressive-like behavior and associated cardiac abnormalities in rats. Along with CUS, RA at a dose of 25 and 50 mg/kg was administered orally to two groups of animals for 40 days. Behavioral tests (forced swim test and sucrose consumption test) and molecular biomarkers (corticosterone and serotonin) were performed. Electrocardiography was performed before CUS (Day 0), Day 20, and Day 40 to study electrocardiogram parameters. Furthermore, changes in body weight, organ weight, tissue lipid peroxidation, glutathione, catalase, cTn-I, MMP-2, and proinflammatory cytokines (TNF-α and IL-6) were estimated. Our results showed that RA treatment caused a reduction in immobility period, adrenal hyperplasia, corticosterone level, tissue lipid peroxidation, cTn-I, MMP-2, proinflammatory cytokines, and QRS complex duration, while an increase in sucrose consumption, brain serotonin level, T-wave width, glutathione, and catalase activity as compared with the CUS-control group. The results of our study proved that RA administration ameliorates CUS-induced depression-associated cardiac abnormalities in rats via serotonergic, oxidative, and inflammatory pathways.
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Affiliation(s)
- Himanshu Verma
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (IIT), Banaras Hindu University (BHU), Varanasi, Uttar Pradesh, India
| | - Naveen Shivavedi
- Shri Ram Group Of Institutions, Faculty of Pharmacy, Jabalpur, Madhya Pradesh, India
| | - Gullanki N V C Tej
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (IIT), Banaras Hindu University (BHU), Varanasi, Uttar Pradesh, India
| | - Mukesh Kumar
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (IIT), Banaras Hindu University (BHU), Varanasi, Uttar Pradesh, India
| | - Prasanta K Nayak
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (IIT), Banaras Hindu University (BHU), Varanasi, Uttar Pradesh, India
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23
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Identification of microRNAs related with neural germ layer lineage-specific progenitors during reprogramming. J Mol Histol 2022; 53:623-634. [DOI: 10.1007/s10735-022-10082-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 05/26/2022] [Indexed: 11/24/2022]
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Wu Q, Duan WZ, Chen JB, Zhao XP, Li XJ, Liu YY, Ma QY, Xue Z, Chen JX. Extracellular Vesicles: Emerging Roles in Developing Therapeutic Approach and Delivery Tool of Chinese Herbal Medicine for the Treatment of Depressive Disorder. Front Pharmacol 2022; 13:843412. [PMID: 35401216 PMCID: PMC8988068 DOI: 10.3389/fphar.2022.843412] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2021] [Accepted: 02/28/2022] [Indexed: 01/29/2023] Open
Abstract
Extracellular vesicles (EVs) are lipid bilayer-delimited particles released by cells, which play an essential role in intercellular communication by delivering cellular components including DNA, RNA, lipids, metabolites, cytoplasm, and cell surface proteins into recipient cells. EVs play a vital role in the pathogenesis of depression by transporting miRNA and effector molecules such as BDNF, IL34. Considering that some herbal therapies exhibit antidepressant effects, EVs might be a practical delivery approach for herbal medicine. Since EVs can cross the blood-brain barrier (BBB), one of the advantages of EV-mediated herbal drug delivery for treating depression with Chinese herbal medicine (CHM) is that EVs can transfer herbal medicine into the brain cells. This review focuses on discussing the roles of EVs in the pathophysiology of depression and outlines the emerging application of EVs in delivering CHM for the treatment of depression.
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Affiliation(s)
- Qian Wu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
- Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Wen-Zhen Duan
- Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Jian-Bei Chen
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Xiao-Peng Zhao
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Xiao-Juan Li
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Yue-Yun Liu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Qing-Yu Ma
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Zhe Xue
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Jia-Xu Chen
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
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Tayab MA, Islam MN, Chowdhury KAA, Tasnim FM. Targeting neuroinflammation by polyphenols: A promising therapeutic approach against inflammation-associated depression. Pharmacotherapy 2022; 147:112668. [DOI: 10.1016/j.biopha.2022.112668] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Revised: 01/12/2022] [Accepted: 01/24/2022] [Indexed: 02/06/2023]
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Baysak E, Guden DS, Aricioglu F, Halaris A. C-reactive protein as a potential biomarker in psychiatric practice: Are we there yet? World J Biol Psychiatry 2022; 23:243-256. [PMID: 34323645 DOI: 10.1080/15622975.2021.1961502] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
OBJECTIVES Serum or plasma levels of C-reactive protein (CRP) and high-sensitivity CRP (hsCRP) are widely used clinical markers of inflammation in other branches of medicine, whereas its clinical use in psychiatry has been limited to research studies. We aimed to assess the possibility of using CRP/hsCRP in psychiatric practice. This is a review and evaluation of various lines of evidence supporting the concept of CRP as a biomarker for psychiatric disorders in certain conditions. METHODS We searched the literature for studies which assessed CRP/hsCRP levels in various psychiatric disorders. RESULTS The accumulating evidence from large studies and meta-analyses allows us to understand the role of CRP in major psychiatric disorders and increase our understanding of specific symptoms and subtypes of disorders. CRP may be considered a 'psychiatric biomarker' which can alert clinicians about neuroinflammation, adverse effects of medications, cardiometabolic status, co-morbidities, and may also predict clinical outcomes and guide optimal treatment.selection. CONCLUSION Although the underlying pathophysiological role of CRP and hsCRP is still elusive and the association between CRP and psychiatric disorders is inconsistent, CRP holds promise to become a psychiatric biomarker.
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Affiliation(s)
- Erensu Baysak
- Department of Psychiatry, Marmara University School of Medicine, Istanbul, Turkey
| | - Demet Sinem Guden
- Department of Basic and Clinical Pharmacology, Istinye University Faculty of Medicine, Istanbul, Turkey
| | - Feyza Aricioglu
- Department of Pharmacology and Psychopharmacology Research Unit, Marmara University School of Pharmacy, Istanbul, Turkey
| | - Angelos Halaris
- Department of Psychiatry and Behavioral Neurosciences, Loyola University Chicago, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, USA
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Ishola IO, Olubodun-Obadun TG, Bakre OA, Ojo ES, Adeyemi OO. Kolaviron ameliorates chronic unpredictable mild stress-induced anxiety and depression: involvement of the HPA axis, antioxidant defense system, cholinergic, and BDNF signaling. Drug Metab Pers Ther 2022; 37:277-287. [PMID: 35218172 DOI: 10.1515/dmpt-2021-0125] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 08/11/2021] [Indexed: 11/15/2022]
Abstract
OBJECTIVES This study sought to investigate the beneficial effect of kolaviron (KV) (a biflavonoid) isolated from Garcinia kola seed on chronic unpredictable mild stress (CUMS)-induced anxiety- and depressive-like behavior. METHODS Male albino mice were randomly divided into six groups (n=8) as follows; Group I: vehicle-control unstressed; Group II: CUMS-control; Group III-V: CUMS + KV 1, 5 or 50 mg/kg, respectively, Group VI: KV (50 mg/kg, p.o.) unstressed mice. Animals were subjected to CUMS for 14 days, followed by estimation of depressive- and anxiety-like behavior from days 14-16. This was followed by biochemical assays for oxidative stress, hypothalamo-pituitary axis, cholinergic, and BDNF signaling. RESULTS CUMS caused significant reduction in time spent in open arms of elevated plus maze test (EPM) and increase in immobility time in tail suspension test (TST) and forced swim test (FST) ameliorated by KV treatments. KV administration also attenuated CUMS-induced malondialdehyde/nitrite generation and decrease in antioxidant enzymes activities in the prefrontal cortex and hippocampus. CUMS increased serum corticosterone, acetylcholinesterase activity, and reduced BDNF level in the PFC and hippocampus were attenuated by KV administration. CONCLUSIONS KV prevented CUMS induced anxiety- and depression-like behavior in mice through enhancement of antioxidant defense mechanisms, neurotrophic factors, and cholinergic systems.
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Affiliation(s)
- Ismail O Ishola
- Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria.,African Centre of Excellence for Drug Research, Herbal Medicine Development and Regulatory Science, Lagos, Nigeria
| | - Taiwo G Olubodun-Obadun
- Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Oluwasayo A Bakre
- Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Emmanuel S Ojo
- Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria.,Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA
| | - Olufunmilayo O Adeyemi
- Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria.,African Centre of Excellence for Drug Research, Herbal Medicine Development and Regulatory Science, Lagos, Nigeria
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Porter GA, O’Connor JC. Brain-derived neurotrophic factor and inflammation in depression: Pathogenic partners in crime? World J Psychiatry 2022; 12:77-97. [PMID: 35111580 PMCID: PMC8783167 DOI: 10.5498/wjp.v12.i1.77] [Citation(s) in RCA: 90] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 07/21/2021] [Accepted: 12/02/2021] [Indexed: 02/06/2023] Open
Abstract
Major depressive disorder is a debilitating disorder affecting millions of people each year. Brain-derived neurotrophic factor (BDNF) and inflammation are two prominent biologic risk factors in the pathogenesis of depression that have received considerable attention. Many clinical and animal studies have highlighted associations between low levels of BDNF or high levels of inflammatory markers and the development of behavioral symptoms of depression. However, less is known about potential interaction between BDNF and inflammation, particularly within the central nervous system. Emerging evidence suggests that there is bidirectional regulation between these factors with important implications for the development of depressive symptoms and anti-depressant response. Elevated levels of inflammatory mediators have been shown to reduce expression of BDNF, and BDNF may play an important negative regulatory role on inflammation within the brain. Understanding this interaction more fully within the context of neuropsychiatric disease is important for both developing a fuller understanding of biological pathogenesis of depression and for identifying novel therapeutic opportunities. Here we review these two prominent risk factors for depression with a particular focus on pathogenic implications of their interaction.
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Affiliation(s)
- Grace A Porter
- Department of Pharmacology, UT Health San Antonio, San Antonio, TX 78229, United States
| | - Jason C O’Connor
- Department of Pharmacology, University of Texas Health San Antonio, San Antonio, TX 78229, United States
- Audie L. Murphy VA Hospital, South Texas Veterans Health System, San Antonio, TX 78229, United States
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Albrakati A, Alsharif KF, Al omairi NE, Alsanie WF, Almalki ASA, Abd Elmageed ZY, Elshopakey GE, Lokman MS, Bauomy AA, Abdel Moneim AE, Kassab RB. Neuroprotective Efficiency of Prodigiosins Conjugated with Selenium Nanoparticles in Rats Exposed to Chronic Unpredictable Mild Stress is Mediated Through Antioxidative, Anti-Inflammatory, Anti-Apoptotic, and Neuromodulatory Activities. Int J Nanomedicine 2021; 16:8447-8464. [PMID: 35002238 PMCID: PMC8722537 DOI: 10.2147/ijn.s323436] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 11/18/2021] [Indexed: 12/13/2022] Open
Abstract
PURPOSE Depression is a mood disorder accompanied by intensive molecular and neurochemical alterations. Currently, available antidepressant therapies are not fully effective and are often accompanied by several adverse impacts. Accordingly, the ultimate goal of this investigation was to clarify the possible antidepressant effects of prodigiosins (PDGs) loaded with selenium nanoparticles (PDGs-SeNPs) in chronic unpredictable mild stress (CUMS)-induced depression-like behavior in rats. METHODS Sixty Sprague Dawley rats were randomly allocated into six groups: control, CUMS group (depression model), fluoxetine (Flu, 10 mg/kg)+CUMS, PDGs+CUMS (300 mg/kg), sodium selenite (Na2SeO3, 400 mg/kg)+CUMS, and PDGs-SeNPs+CUMS (200 mg/kg). All treatments were applied orally for 28 consecutive days. RESULTS PDGs-SeNPs administration prevented oxidative insults in hippocampal tissue, as demonstrated by decreased oxidant levels (nitric oxide and malondialdehyde) and elevated innate antioxidants (glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase), in addition to the upregulated expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in rats exposed to CUMS. Additionally, PDGs-SeNPs administration suppressed neuroinflammation in hippocampal tissue, as determined by the decreased production of pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1β, and interleukin-6), increased anti-inflammatory cytokine interleukin-10, and decreased inflammatory mediators (prostaglandin E2, cyclooxygenase-2, and nuclear factor kappa B). Moreover, PDGs-SeNPs administration in stressed rats inhibited neuronal loss and the development of hippocampal apoptosis through enhanced levels of B cell lymphoma 2 and decreased levels of caspase 3 and Bcl-2-associated X protein. Interestingly, PDGs-SeNPs administration improved hormonal levels typically disrupted by CUMS exposure and significantly modulated hippocampal levels of monoamines, brain-derived neurotrophic factor, monoamine oxidase, and acetylcholinesterase activities, in addition to upregulating the immunoreactivity of glial fibrillary acidic protein in CUMS model rats. CONCLUSION PDGs-SeNPs may serve as a prospective antidepressant candidate due to their potent antioxidant, anti-inflammatory, and neuroprotective potential.
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Affiliation(s)
- Ashraf Albrakati
- Department of Human Anatomy, College of Medicine, Taif University, Taif, Saudi Arabia
| | - Khalaf F Alsharif
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia
| | - Naif E Al omairi
- Department of Internal Medicine, College of Medicine, Taif University, Taif, Saudi Arabia
| | - Walaa F Alsanie
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia
| | | | - Zakaria Y Abd Elmageed
- Department of Pharmacology, Edward via College of Osteopathic Medicine, University of Louisiana at Monroe, Monroe, LA, USA
| | - Gehad E Elshopakey
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
| | - Maha S Lokman
- Biology Department, College of Science and Humanities, Prince Sattam bin Abdul Aziz University, Alkharj, Saudi Arabia
- Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt
| | - Amira A Bauomy
- Department of Science Laboratories, College of Science and Arts, Qassim University, ArRassAl-Qassim, Saudi Arabia
| | - Ahmed E Abdel Moneim
- Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt
| | - Rami B Kassab
- Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt
- Biology Department, Faculty of Science and Arts, Al Baha University, Al Makhwah Branch, Al Baha, Saudi Arabia
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Abdelzaher WY, Mohammed HH, Welson NN, Batiha GES, Baty RS, Abdel-Aziz AM. Rivaroxaban Modulates TLR4/Myd88/NF-Kβ Signaling Pathway in a Dose-Dependent Manner With Suppression of Oxidative Stress and Inflammation in an Experimental Model of Depression. Front Pharmacol 2021; 12:715354. [PMID: 34630092 PMCID: PMC8497790 DOI: 10.3389/fphar.2021.715354] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 08/10/2021] [Indexed: 01/10/2023] Open
Abstract
Depression is a common mental illness leading to upset or anxiety, with a high incidence rate in the world. Depression can lead to suicidal thoughts and behavior. The present study aimed to evaluate the effect of the direct oral anticoagulant rivaroxaban (RVX), in the model of depression induced by chronic unpredicted mild stress (CUMS) in rats. Fifty-six male Wister rats were randomly divided into seven experimental groups (8 rats/group); Group 1: Control group given vehicle per oral (p.o.), Group 2: RVXL-control group (received rivaroxaban 20 mg/kg/day, p.o..), Group 3: RVXH-control group (received rivaroxaban 30 mg/kg/day, p.o.), Group 4: chronic unpredictable mild stress (CUMS) group, Group 5: FLX-treated CUMS group (received fluoxetine 10 mg/kg/day, p.o..), Group 6: RVXL-treated CUMS group (received rivaroxaban 20 mg/kg/day, p.o.), and Group 7: RVXH-treated CUMS group (received rivaroxaban 30 mg/kg/day, p.o.). The rats received the drugs from the first day of the experiment and continued till 4 weeks-the duration of the study. The following were measured: monoamine neurotransmitters, malondialdehyde (MDA), total nitrite/nitrate (NOx), reduced glutathione (GSH), superoxide dismutase (SOD), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor-A (VEGF-A). A forced swimming test (FST) was done. Furthermore, histological changes and glial fibrillary acidic protein (GFAP) immunoexpression were evaluated. CUMS showed a significant decrease in hypothalamic neurotransmitters, hippocampal GSH, SOD, BNDF, and VEGF-A with a significant increase in hippocampal MDA, NOx, NF-kβ, Myd88, TLR4, TNF-α, and GFAP immunoexpression. RVX showed significant improvement in all parameters (p -value < 0.0001). In conclusion, RVX in a dose-dependent manner possesses potent ameliorative effects against depression by reducing the oxidative stress and inflammatory process, through the regulation of the TLR4/Myd88/NF-kβ signaling pathway.
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Affiliation(s)
| | - Hanaa H Mohammed
- Department of Histology, Faculty of Medicine, Minia University, Minia, Egypt
| | - Nermeen N Welson
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt
| | - Roua S Baty
- Department of Biotechnology, College of Science, Taif University, Taif, Saudi Arabia
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Mikulska J, Juszczyk G, Gawrońska-Grzywacz M, Herbet M. HPA Axis in the Pathomechanism of Depression and Schizophrenia: New Therapeutic Strategies Based on Its Participation. Brain Sci 2021; 11:1298. [PMID: 34679364 PMCID: PMC8533829 DOI: 10.3390/brainsci11101298] [Citation(s) in RCA: 168] [Impact Index Per Article: 42.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 09/24/2021] [Accepted: 09/24/2021] [Indexed: 12/27/2022] Open
Abstract
The hypothalamic-pituitary-adrenal (HPA) axis is involved in the pathophysiology of many neuropsychiatric disorders. Increased HPA axis activity can be observed during chronic stress, which plays a key role in the pathophysiology of depression. Overactivity of the HPA axis occurs in major depressive disorder (MDD), leading to cognitive dysfunction and reduced mood. There is also a correlation between the HPA axis activation and gut microbiota, which has a significant impact on the development of MDD. It is believed that the gut microbiota can influence the HPA axis function through the activity of cytokines, prostaglandins, or bacterial antigens of various microbial species. The activity of the HPA axis in schizophrenia varies and depends mainly on the severity of the disease. This review summarizes the involvement of the HPA axis in the pathogenesis of neuropsychiatric disorders, focusing on major depression and schizophrenia, and highlights a possible correlation between these conditions. Although many effective antidepressants are available, a large proportion of patients do not respond to initial treatment. This review also discusses new therapeutic strategies that affect the HPA axis, such as glucocorticoid receptor (GR) antagonists, vasopressin V1B receptor antagonists and non-psychoactive CB1 receptor agonists in depression and/or schizophrenia.
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Affiliation(s)
| | | | - Monika Gawrońska-Grzywacz
- Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, 8b Jaczewskiego Street, 20-090 Lublin, Poland; (J.M.); (G.J.); (M.H.)
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Song L, Wu X, Wang J, Guan Y, Zhang Y, Gong M, Wang Y, Li B. Antidepressant effect of catalpol on corticosterone-induced depressive-like behavior involves the inhibition of HPA axis hyperactivity, central inflammation and oxidative damage probably via dual regulation of NF-κB and Nrf2. Brain Res Bull 2021; 177:81-91. [PMID: 34500039 DOI: 10.1016/j.brainresbull.2021.09.002] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 09/02/2021] [Accepted: 09/03/2021] [Indexed: 12/24/2022]
Abstract
This study aimed to investigate the antidepressant effect and mechanism of catalpol on corticosterone (CORT)-induced depressive-like behavior in mice for the first time. As a result, CORT injection induced depressive-like behaviors of mice in behavioral tests, aggravated the serum CORT, adrenocorticotropic hormone, and corticotropin-releasing hormone levels, and conspicuously elevated the phosphorylations of nuclear factor kappa-B (NF-κB) in the hippocampus and frontal cortex, and down-regulated the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2). Furthermore, CORT exposure dramatically augmented the levels of inflammatory factors (interleukin-1β, tumor necrosis factor-α, nitric oxide synthase, and nitric oxide) and lipid peroxidation product malondialdehyde, and attenuated the levels of antioxidants including reduced glutathione, glutathione S-transferase, total superoxide dismutase, and heme oxygenase-1 in the mouse hippocampus and frontal cortex. On the contrary, catalpol administration markedly suppressed the abnormalities of the above indicators. From the overall results, this study displayed that catalpol exerted a beneficial effect on CORT-induced depressive-like behavior in mice possibly via the inhibition of hypothalamus-pituitary-adrenal (HPA) axis hyperactivity, central inflammation and oxidative damage at least partially through dual regulation of NF-κB and Nrf2.
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Affiliation(s)
- Lingling Song
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China
| | - Xiaohui Wu
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China
| | - Junming Wang
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China; Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, 450046, China.
| | - Yuechen Guan
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China
| | - Yueyue Zhang
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China
| | - Mingzhu Gong
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China
| | - Yanmei Wang
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China
| | - Bingyin Li
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China
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Martínez-Damas MG, Genis-Mendoza AD, Pérez-de la Cruz V, Canela-Tellez GD, Jiménez-Estrada I, Nicolini-Sanchez JH, Ramos-Chávez LA, García S, Ramírez-Ramírez M, Coral-Vázquez RM. Epicatechin treatment generates resilience to chronic mild stress-induced depression in a murine model. Physiol Behav 2021; 238:113466. [PMID: 34033845 DOI: 10.1016/j.physbeh.2021.113466] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 05/18/2021] [Accepted: 05/20/2021] [Indexed: 10/21/2022]
Abstract
Several studies have proposed that cocoa products-enriched in flavonoids reduce anxiety and depressive symptoms. (-)-Epicatechin (Epi), a flavonoid present in high concentration in cocoa, has been associated with many dark chocolate effects and has been postulated as an exercise mimetic. Physical exercise is used as an adjuvant treatment for many depressive patients. This study aimed to evaluate the impact of Epi on resilience in depression-like behavior in a murine model. Male mice were randomly selected and divided into four groups (n = 8/group). Beginning at the age of 8-9 weeks, the mice were subjected to Chronic Mild Stress (CMS) and/or treatment Epi for five weeks. Epi was administered by oral gavage twice daily/5 weeks. The control group was housed in conditions without stress and Epi treatment. Depressive behavior was evaluated by sucrose preference and open field tests. Interestingly, Epi reduced anhedonia and anxiogenic behavior in the murine stress model. These results suggest that Epi induces resilience to stress-induced depression. Furthermore, our findings propose that muscles respond to Epi treatment according to their type of metabolism and that kynurenine aminotransferases (KATs) could play a role in modulating this response.
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Affiliation(s)
- Mirna Guadalupe Martínez-Damas
- Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, México; Subdirección de Enseñanza e Investigación, Centro Médico Nacional "20 de Noviembre", Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Ciudad de México, México
| | - Alma Delia Genis-Mendoza
- Laboratorio de Genómica de Enfermedades Psiquiátricas y Neurodegenerativas, Instituto Nacional de Medicina Genómica, Ciudad de México, México
| | - Verónica Pérez-de la Cruz
- Laboratorio de Neurobioquimica y Conducta, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, S.S.A. Ciudad de México, México
| | - Gabriel Daniel Canela-Tellez
- Subdirección de Enseñanza e Investigación, Centro Médico Nacional "20 de Noviembre", Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Ciudad de México, México
| | - Ismael Jiménez-Estrada
- Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México, México
| | - José Humberto Nicolini-Sanchez
- Laboratorio de Genómica de Enfermedades Psiquiátricas y Neurodegenerativas, Instituto Nacional de Medicina Genómica, Ciudad de México, México
| | - Lucio Antonio Ramos-Chávez
- Departamento de Neuroquímica, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente, Ciudad de México, México
| | - Silvia García
- Centro Médico Nacional "20 de Noviembre", Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Ciudad de México, México
| | - Magally Ramírez-Ramírez
- Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, México; Subdirección de Enseñanza e Investigación, Centro Médico Nacional "20 de Noviembre", Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Ciudad de México, México
| | - Ramón Mauricio Coral-Vázquez
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, México; Subdirección de Enseñanza e Investigación, Centro Médico Nacional "20 de Noviembre", Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Ciudad de México, México.
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Berding K, Vlckova K, Marx W, Schellekens H, Stanton C, Clarke G, Jacka F, Dinan TG, Cryan JF. Diet and the Microbiota-Gut-Brain Axis: Sowing the Seeds of Good Mental Health. Adv Nutr 2021; 12:1239-1285. [PMID: 33693453 PMCID: PMC8321864 DOI: 10.1093/advances/nmaa181] [Citation(s) in RCA: 153] [Impact Index Per Article: 38.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 12/18/2020] [Accepted: 12/21/2020] [Indexed: 02/06/2023] Open
Abstract
Over the past decade, the gut microbiota has emerged as a key component in regulating brain processes and behavior. Diet is one of the major factors involved in shaping the gut microbiota composition across the lifespan. However, whether and how diet can affect the brain via its effects on the microbiota is only now beginning to receive attention. Several mechanisms for gut-to-brain communication have been identified, including microbial metabolites, immune, neuronal, and metabolic pathways, some of which could be prone to dietary modulation. Animal studies investigating the potential of nutritional interventions on the microbiota-gut-brain axis have led to advancements in our understanding of the role of diet in this bidirectional communication. In this review, we summarize the current state of the literature triangulating diet, microbiota, and host behavior/brain processes and discuss potential underlying mechanisms. Additionally, determinants of the responsiveness to a dietary intervention and evidence for the microbiota as an underlying modulator of the effect of diet on brain health are outlined. In particular, we emphasize the understudied use of whole-dietary approaches in this endeavor and the need for greater evidence from clinical populations. While promising results are reported, additional data, specifically from clinical cohorts, are required to provide evidence-based recommendations for the development of microbiota-targeted, whole-dietary strategies to improve brain and mental health.
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Affiliation(s)
| | | | - Wolfgang Marx
- Deakin University, iMPACT – the Institute for Mental and Physical Health and Clinical Translation, Food & Mood Centre, School of Medicine, Barwon Health, Geelong, VIC,Australia
| | - Harriet Schellekens
- APC Microbiome Ireland, Cork, Ireland
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Catherine Stanton
- APC Microbiome Ireland, Cork, Ireland
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
| | - Gerard Clarke
- APC Microbiome Ireland, Cork, Ireland
- Department of Psychiatry and Neurobehavioural Sciences, University College Cork, Cork, Ireland
| | - Felice Jacka
- Deakin University, iMPACT – the Institute for Mental and Physical Health and Clinical Translation, Food & Mood Centre, School of Medicine, Barwon Health, Geelong, VIC,Australia
- Centre for Adolescent Health, Murdoch Children's Research Institute, Parkville, VIC, Australia
- Black Dog Institute, Randwick, NSW, Australia
- College of Public Health, Medical & Veterinary Sciences, James Cook University, Douglas, QLD, Australia
| | - Timothy G Dinan
- APC Microbiome Ireland, Cork, Ireland
- Department of Psychiatry and Neurobehavioural Sciences, University College Cork, Cork, Ireland
| | - John F Cryan
- APC Microbiome Ireland, Cork, Ireland
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
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35
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Xu JX, Fang K, Gao XR, Liu S, Ge JF. Resveratrol Protects SH-SY5Y Cells Against Oleic Acid-Induced Glucolipid Metabolic Dysfunction and Cell Injuries Via the Wnt/β-Catenin Signalling Pathway. Neurochem Res 2021; 46:2936-2947. [PMID: 34260003 DOI: 10.1007/s11064-021-03398-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 07/05/2021] [Accepted: 07/07/2021] [Indexed: 12/23/2022]
Abstract
Resveratrol (RES) is a polyphenol with diverse beneficial biological and pharmacological activities, and our previous results have demonstrated its neuroprotective effects in several metabolic diseases, including non-alcoholic fatty liver disease. The aim of the present study is to investigate the potential effect of RES against oleic acid (OA)-induced cell injuries in SH-SY5Y cells and explore the possible mechanism. Based on the dose- and time-dependent effects of OA on cell proliferation and LDH release, SH-SY5Y cells were challenged with OA and incubated with or without RES (10-5-10-9 mM) or sitagliptin (STG, 10-7 mM). Lipid accumulation, SREBP1 and PPARα protein expression, glucose consumption and IRS1, AKT, ERK phosphorylation under insulin stimulation, and ROS production were detected. The protein expression of brain-derived neurotrophic factor (BDNF), Copine 6, and key molecules in the Wnt/β-catenin signalling pathway were measured via western blot. The expression of Wnt 1 was also measured via immunofluorescence staining. The results showed that RES treatment could alleviate the neurotoxicity induced by OA, as indicated by the increased cell proliferation and the decreased concentration of LDH in the supernatant. The increased lipid deposition and protein expression of SREBP1 and PPARα induced by OA was also reversed by treatment with RES. Moreover, RES could upregulate glucose consumption and the protein expression of phosphorylated IRS1, AKT, ERK and reduced ROS production in OA-induced SH-SY5Y cells. Furthermore, RES treatment reversed the imbalanced protein expression of BDNF, Copine 6, p-β-catenin, and Wnt 1 in SH-SY5Y cells induced by OA and decreased the hyperexpression of p-GSK3β. However, these effects were suppressed by DKK1, which is a specific antagonist of the Wnt signalling pathway. These results suggested that RES has a neuroprotective effect against OA-induced cell injury and dysfunctional glucolipid metabolism, and the mechanism might involve its ability to regulate oxidative stress and insulin resistance via the Wnt/β-catenin signalling pathway.
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Affiliation(s)
- Jing-Xian Xu
- School of Pharmacy, Anhui Medical University, 81 Mei-Shan Road, Hefei, 230032, Anhui, China.,Anhui Provincial Laboratory of Inflammatory and Immune Disease, Anhui Institute of Innovative Drugs, Hefei, China.,The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China
| | - Ke Fang
- School of Pharmacy, Anhui Medical University, 81 Mei-Shan Road, Hefei, 230032, Anhui, China.,Anhui Provincial Laboratory of Inflammatory and Immune Disease, Anhui Institute of Innovative Drugs, Hefei, China.,The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China
| | - Xin-Ran Gao
- School of Pharmacy, Anhui Medical University, 81 Mei-Shan Road, Hefei, 230032, Anhui, China.,Anhui Provincial Laboratory of Inflammatory and Immune Disease, Anhui Institute of Innovative Drugs, Hefei, China.,The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China
| | - Sen Liu
- School of Pharmacy, Anhui Medical University, 81 Mei-Shan Road, Hefei, 230032, Anhui, China.,Anhui Provincial Laboratory of Inflammatory and Immune Disease, Anhui Institute of Innovative Drugs, Hefei, China.,The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China
| | - Jin-Fang Ge
- School of Pharmacy, Anhui Medical University, 81 Mei-Shan Road, Hefei, 230032, Anhui, China. .,Anhui Provincial Laboratory of Inflammatory and Immune Disease, Anhui Institute of Innovative Drugs, Hefei, China. .,The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China.
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36
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Rana T, Behl T, Sehgal A, Sachdeva M, Mehta V, Sharma N, Singh S, Bungau S. Exploring Sonic Hedgehog Cell Signaling in Neurogenesis: Its Potential Role in Depressive Behavior. Neurochem Res 2021; 46:1589-1602. [PMID: 33786718 DOI: 10.1007/s11064-021-03307-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 03/01/2021] [Accepted: 03/17/2021] [Indexed: 12/26/2022]
Abstract
Depression is the most prevalent form of neuropsychiatric disorder affecting all age groups globally. As per the estimation of the World Health Organization (WHO), depression will develop into the foremost reason for disability globally by the year 2030. The primary neurobiological mechanism implicated in depression remains ambiguous; however, dysregulation of molecular and signaling transductions results in depressive disorders. Several theories have been developed to explain the pathogenesis of depression, however, none of them completely explained all aspects of depressive-pathogenesis. In the current review, we aimed to explore the role of the sonic hedgehog (Shh) signaling pathway in the development of the depressive disorder and its potential as the therapeutic target. Shh signaling has a crucial function in neurogenesis and neural tube patterning during the development of the central nervous system (CNS). Shh signaling performs a basic function in embryogenesis and hippocampal neurogenesis. Moreover, antidepressants are also known to enhance neurogenesis in the hippocampus, which further suggests the potential of Shh signaling. Furthermore, there is decreased expression of a glioma-associated oncogene (Gli1) and Smoothened (Smo) in depression. Moreover, antidepressants also regulate brain-derived neurotrophic factor (BDNF) and wingless protein (Wnt) signaling, therefore, Shh may be implicated in the pathogenesis of the depressive disorder. Deregulation of Shh signaling in CNS results in neurological disorders such as depression.
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Affiliation(s)
- Tarapati Rana
- Government Pharmacy College, Seraj, Distt. Mandi, Himachal Pradesh, India.,Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Tapan Behl
- Chitkara College of Pharmacy, Chitkara University, Punjab, India.
| | - Aayush Sehgal
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Monika Sachdeva
- Fatimah College of Health Sciences, Al Ain, United Arab Emirates
| | - Vineet Mehta
- Government College of Pharmacy, Rohru, Distt. Shimla, Himachal Pradesh, India
| | - Neelam Sharma
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Sukhbir Singh
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania
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Gastrodiae Rhizoma Water Extract Ameliorates Hypothalamic-Pituitary-Adrenal Axis Hyperactivity and Inflammation Induced by Chronic Unpredictable Mild Stress in Rats. BIOMED RESEARCH INTERNATIONAL 2021; 2020:8374614. [PMID: 32596383 PMCID: PMC7305529 DOI: 10.1155/2020/8374614] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Accepted: 05/05/2020] [Indexed: 12/18/2022]
Abstract
Gastrodiae Rhizoma is a highly valuable traditional herbal medicine commonly used to treat neurological disorders. The present study is designed to determine the antidepressant-like effect of the Gastrodiae Rhizoma water extract (GRWE) on a depression model and the potential mechanisms. The chronic unpredictable mild stress (CUMS) rat model was used to induce depression. The sucrose preference test, open field test, forced swimming test, and tail suspension test were performed to assess the depressive-like behaviors, respectively. Hypothalamic-pituitary-adrenal (HPA) function was measured via plasma corticosterone (CORT), adrenocorticotrophic hormone (ACTH), hypothalamic corticotropin-releasing factor (CRF), and glucocorticoid receptor (GR) concentrations. Plasma concentrations of proinflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were also evaluated. The results showed that GRWE significantly attenuates the behavioral abnormalities in CUMS rats, as shown by elevated sucrose consumption, raised locomotor activity, and reduced immobility duration. Moreover, GRWE treatment reduced CORT, ACTH, CRF, and GR levels and decreased the plasma IL-1β, IL-6, and TNF-α concentrations. These findings indicate that GRWE improves depressive behaviors in a chronic stress model of rats; its effect may be ascribed to the modulation of the HPA axis activity and inflammatory response.
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38
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Autophagy status as a gateway for stress-induced catecholamine interplay in neurodegeneration. Neurosci Biobehav Rev 2021; 123:238-256. [PMID: 33497785 DOI: 10.1016/j.neubiorev.2021.01.015] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 01/08/2021] [Accepted: 01/09/2021] [Indexed: 12/13/2022]
Abstract
The catecholamine-containing brainstem nuclei locus coeruleus (LC) and ventral tegmental area (VTA) are critically involved in stress responses. Alterations of catecholamine systems during chronic stress may contribute to neurodegeneration, including cognitive decline. Stress-related catecholamine alterations, while contributing to anxiety and depression, might accelerate neuronal degeneration by increasing the formation of toxic dopamine and norepinephrine by-products. These, in turn, may impair proteostasis within a variety of cortical and subcortical areas. In particular, the molecular events governing neurotransmission, neuroplasticity, and proteostasis within LC and VTA affect a variety of brain areas. Therefore, we focus on alterations of autophagy machinery in these nuclei as a relevant trigger in this chain of events. In fact, these catecholamine-containing areas are mostly prone to autophagy-dependent neurodegeneration. Thus, we propose a dynamic hypothesis according to which stress-induced autophagy alterations within the LC-VTA network foster a cascade towards early neurodegeneration within these nuclei.
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Ahmad MH, Rizvi MA, Fatima M, Mondal AC. Pathophysiological implications of neuroinflammation mediated HPA axis dysregulation in the prognosis of cancer and depression. Mol Cell Endocrinol 2021; 520:111093. [PMID: 33253761 DOI: 10.1016/j.mce.2020.111093] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 11/02/2020] [Accepted: 11/20/2020] [Indexed: 02/07/2023]
Abstract
Cancer patients are more likely to develop depressive symptoms and show a poor prognosis compared to the normal healthy individuals. Cancer occurrence and the anticancer treatments result in the pro-inflammatory cytokines-mediated inflammation, which dysregulates the HPA-axis activity that may result in depression-like behaviour. Conversely, depression causes the activation of the HPA-axis that results in the downstream release of endogenous glucocorticoids which may result in depressive signs and symptoms in some cancer patients. Depression may also result in non-adherence to treatment and increased mortality in cancer patients. In this review, we have focused on the role of neuroimmune axis and hyperactive HPA-axis in case of both cancer and depression. Therefore, therapeutics targeting the HPA-axis dysregulation could be effective in ameliorating symptoms of depression in cancer patients.
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Affiliation(s)
- Mir Hilal Ahmad
- Laboratory of Cellular and Molecular Neurobiology, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India; Department of Biosciences, Jamia Millia Islamia, New Delhi, 110025, India
| | | | - Mahino Fatima
- Laboratory of Cellular and Molecular Neurobiology, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India
| | - Amal Chandra Mondal
- Laboratory of Cellular and Molecular Neurobiology, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
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40
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Chinese Herbal Medicine for the Treatment of Depression: Effects on the Neuroendocrine-Immune Network. Pharmaceuticals (Basel) 2021; 14:ph14010065. [PMID: 33466877 PMCID: PMC7830381 DOI: 10.3390/ph14010065] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 01/10/2021] [Accepted: 01/11/2021] [Indexed: 02/06/2023] Open
Abstract
The neuroimmune and neuroendocrine systems are two critical biological systems in the pathogenesis of depression. Clinical and preclinical studies have demonstrated that the activation of the neuroinflammatory response of the immune system and hyperactivity of the hypothalamus–pituitary–adrenal (HPA) axis of the neuroendocrine system commonly coexist in patients with depression and that these two systems bidirectionally regulate one another through neural, immunological, and humoral intersystem interactions. The neuroendocrine-immune network poses difficulties associated with the development of antidepressant agents directed toward these biological systems for the effective treatment of depression. On the other hand, multidrug and multitarget Chinese Herbal Medicine (CHM) has great potential to assist in the development of novel medications for the systematic pharmacotherapy of depression. In this narrative essay, we conclusively analyze the mechanisms of action of CHM antidepressant constituents and formulas, specifically through the modulation of the neuroendocrine-immune network, by reviewing recent preclinical studies conducted using depressive animal models. Some CHM herbal constituents and formulas are highlighted as examples, and their mechanisms of action at both the molecular and systems levels are discussed. Furthermore, we discuss the crosstalk of these two biological systems and the systems pharmacology approach for understanding the system-wide mechanism of action of CHM on the neuroendocrine-immune network in depression treatment. The holistic, multidrug, and multitarget nature of CHM represents an excellent example of systems medicine in the effective treatment of depression.
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Geng R, Li H, Wang H, Ye C, Mao Y, Huang X. Venlafaxine Inhibits the Apoptosis of SHSY-5Y Cells Through Active Wnt/β-Catenin Signaling Pathway. Neuropsychiatr Dis Treat 2021; 17:1145-1151. [PMID: 33907406 PMCID: PMC8071209 DOI: 10.2147/ndt.s294998] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 04/01/2021] [Indexed: 11/23/2022] Open
Abstract
OBJECTIVE This study aimed to explore the mechanism of venlafaxine in regulating the apoptosis of SHSY-5Y cells induced by hypoxia. METHODS The CoCl2-induced neuronal hypoxia model was established based on SHSY-5Y cells. The morphology and related protein expression of SHSY-5Y cells were detected by qPCR, ELISA and Western blot. RESULTS Under the condition of hypoxia-induced by CoCl2, the expression of HIF-1α in SHSY-5Y cells was up-regulated and the expression of β-catenin was down-regulated. After adding siRNA targeting HIF-1 α to the culture cell system, down-regulation of β -catenin expression in SHSY-5Y cells was restored. This confirmed the existence of the "hypoxia-HIF-1α-Wnt/β-catenin-depression" axis. Further studies have shown that venlafaxine can alleviate neuronal apoptosis induced by hypoxia by upregulating the Wnt/β-catenin signaling pathway. CONCLUSION Venlafaxine regulates apoptosis induced by hypoxia through the Wnt/β-catenin signaling pathway, which provides a new theoretical basis for the treatment of depression.
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Affiliation(s)
- Ruijie Geng
- Department of Psychological Medicine, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Haibin Li
- Department of Psychological Medicine, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Hao Wang
- Teaching Center of Experimental Medicine, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Chenyu Ye
- Department of Psychological Medicine, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Yemeng Mao
- Department of Pharmacy, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China
| | - Xiao Huang
- Department of Psychological Medicine, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Department of Psychological Medicine, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, Fujian, People's Republic of China
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Shayganfard M. Molecular and biological functions of resveratrol in psychiatric disorders: a review of recent evidence. Cell Biosci 2020; 10:128. [PMID: 33292508 PMCID: PMC7648996 DOI: 10.1186/s13578-020-00491-3] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Accepted: 10/29/2020] [Indexed: 12/20/2022] Open
Abstract
Mental disorders including depression, anxiety, schizophrenia, autism spectrum disorders, bipolar and etc. have a considerable proportion of global disorder burden. Many nutritional psychiatry investigations have been conducted to evaluate the relationship between several individual nutrients such as herbal compounds with mental health. Resveratrol, a famous polyphenol compound, is known as an antioxidant, anti-inflammatory, anti-apoptotic, and neuroprotective agent regulating the function of brain and improves the behavioral factors associated with learning, anxiety, depression, and memory. In addition, this natural compound can cross the blood–brain barrier representing neurological influences. The pharmacological interest of utilizing resveratrol in mental disorders is due to its anti-inflammatory and antioxidant features. The aim of this paper was to review the studies evaluated the potential effects of resveratrol on mental disorders.
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Affiliation(s)
- Mehran Shayganfard
- Department of Psychiatry, Arak University of Medical Sciences, Arak, Iran.
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43
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Effects of Transcutaneous Auricular Vagus Nerve Stimulation on Peripheral and Central Tumor Necrosis Factor Alpha in Rats with Depression-Chronic Somatic Pain Comorbidity. Neural Plast 2020; 2020:8885729. [PMID: 33144854 PMCID: PMC7599410 DOI: 10.1155/2020/8885729] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 09/06/2020] [Accepted: 09/24/2020] [Indexed: 02/07/2023] Open
Abstract
Depression and pain disorders share a high degree of comorbidity. Inflammatory mechanisms play an important role in the pathogenesis of depression-chronic somatic pain comorbidity. In this study, we investigated the effects of acupuncture on blood and brain regional tumor necrosis factor alpha (TNF-α) in rats with depression and chronic somatic pain comorbidity. Forty Sprague-Dawley rats were randomly divided into the following 4 groups with 10 each: control, model, model treated with transcutaneous auricular vagus nerve stimulation (taVNS), and model treated with electroacupuncture (EA). Chronic unpredictable mild stress (CUMS) with chronic constriction injury of the sciatic nerve (CCI) was used to produce depression and chronic somatic pain comorbidity in the latter 3 groups. The rats of the taVNS and EA groups received, respectively, taVNS and EA at ST 36 for 28 days. Pain intensity was measured using a mechanical withdrawal threshold and thermal stimulation latency once biweekly. Depressive behavior was examined using a sucrose preference test at baseline and the end of modeling and intervention. The level of plasma TNF-α and the expression of TNF-α in the prefrontal cortex (PFC), hippocampus, amygdala, and hypothalamus were measured. While CUMS plus CCI produced remarkable depression-like behavior and pain disorders, EA and taVNS significantly improved depression and reduced pain intensity. CUMS plus CCI also resulted in a significant increase in plasma TNF-α level and the expression in all brain regions examined compared to the intact controls. Both EA and taVNS interventions, however, suppressed the elevated level of TNF-α. These results suggest that EA and taVNS have antidepressant and analgesic effects. Such effects may be associated with the suppression of TNF-α-related neuroinflammation.
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Amisulpride alleviates chronic mild stress-induced cognitive deficits: Role of prefrontal cortex microglia and Wnt/β-catenin pathway. Eur J Pharmacol 2020; 885:173411. [DOI: 10.1016/j.ejphar.2020.173411] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 07/22/2020] [Accepted: 07/23/2020] [Indexed: 12/11/2022]
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Fonseca-Santos B, Chorilli M. The uses of resveratrol for neurological diseases treatment and insights for nanotechnology based-drug delivery systems. Int J Pharm 2020; 589:119832. [PMID: 32877730 DOI: 10.1016/j.ijpharm.2020.119832] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 08/14/2020] [Accepted: 08/26/2020] [Indexed: 02/06/2023]
Abstract
Neurological disorders have been growing in recent years and are highly prevalent globally. Resveratrol (RES) is a natural product from plant sources such as grape skins. This compound has shown biological activity in many diseases, in particular, those that act on the central nervous system. The mechanism of action and the key points in neurological disorders were described and show the targeted mechanism of action. Due to the insolubility of this compound; the use of nanotechnology-based systems has been proposed for the incorporation of RES and RES-loaded nanocarriers have been designed for intranasal administration, oral or parenteral routes to deliver it to the brain. In general, these nanosystems have shown to be effective in many studies, pharmacological and pharmacokinetic assays, as well as some cell studies. The outcomes show that RES has been reported in human clinical trials for some neurological diseases, although no studies were performed in humans using nanocarriers, animal and/or cellular models have been reported to show good results regarding therapeutics on neurological diseases. Thus, the use of this nutraceutical has shown true for neurological diseases and its loading into nanocarriers displaying good results on the stability, delivery and targeting to the brain.
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Affiliation(s)
- Bruno Fonseca-Santos
- São Paulo State University - UNESP, School of Pharmaceutical Sciences, Department of Drugs and Medicines, Araraquara, São Paulo 14801-903, Brazil
| | - Marlus Chorilli
- São Paulo State University - UNESP, School of Pharmaceutical Sciences, Department of Drugs and Medicines, Araraquara, São Paulo 14801-903, Brazil.
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Effects of lithium on cytokine neuro-inflammatory mediators, Wnt/β-catenin signaling and microglial activation in the hippocampus of chronic mild stress-exposed rats. Toxicol Appl Pharmacol 2020; 399:115073. [DOI: 10.1016/j.taap.2020.115073] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 05/11/2020] [Accepted: 05/22/2020] [Indexed: 12/29/2022]
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Donoso F, Egerton S, Bastiaanssen TFS, Fitzgerald P, Gite S, Fouhy F, Ross RP, Stanton C, Dinan TG, Cryan JF. Polyphenols selectively reverse early-life stress-induced behavioural, neurochemical and microbiota changes in the rat. Psychoneuroendocrinology 2020; 116:104673. [PMID: 32334345 DOI: 10.1016/j.psyneuen.2020.104673] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 02/07/2020] [Accepted: 03/25/2020] [Indexed: 01/06/2023]
Abstract
There is a growing emphasis on the role of the microbiota-gut-brain axis as modulator of host behaviour and as therapeutic target for neuropsychiatric disorders. In addition, accumulating evidence suggests that early-life stress can exert long-lasting changes on the brain and microbiota, and this early adversity is associated with increased risk for developing depression in later life. The maternal separation (MS) model in rats is a robust paradigm to study the effects of early-life stress on the microbiota-gut-brain axis. Recently, we have shown that polyphenols, naturally occurring compounds associated with several health benefits, have anti-stress effects in in vitro models. In this study, we assess the therapeutic potential of a variety of both flavonoid and non-flavonoid polyphenols in reversing the impact of MS on behaviour and the microbiota-gut-brain axis. Rats underwent a dietary intervention with the naturally-derived polyphenols xanthohumol and quercetin, as well as with a phlorotannin extract for 8 weeks. Treatment with polyphenols prevented the depressive- and anxiety-like behaviours induced by MS, where xanthohumol effects were correlated with rescue of BDNF plasma levels. In addition, MS resulted in altered brain levels of 5-hydroxyindoleacetic acid (5-HIAA) and dopamine, accompanied by abnormal elevation of plasma corticosterone. Although polyphenols did not reverse neurotransmitter imbalance, xanthohumol normalised corticosterone levels in MS rats. Finally, we explored the impact of MS and polyphenolic diets on the gut microbiota. We observed profound changes in microbial composition and diversity produced by MS condition and by xanthohumol treatment. Moreover, functional prediction analysis revealed that MS results in altered enrichment of pathways associated with microbiota-brain interactions that are significantly reversed by xanthohumol treatment. These results suggest that naturally-derived polyphenols exert antidepressant-like effects in MS rats, which mechanisms could be potentially mediated by HPA regulation, BDNF levels rescue and modulation of the microbiota-gut-brain axis.
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Affiliation(s)
- Francisco Donoso
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Psychiatry & Neurobehavioural Science, University College Cork, Cork, Ireland
| | - Sian Egerton
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland; School of Biological, Earth and Environmental Science, University College, Cork, Ireland
| | - Thomaz F S Bastiaanssen
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland
| | - Patrick Fitzgerald
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland
| | - Snehal Gite
- Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland
| | - Fiona Fouhy
- Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland
| | - R Paul Ross
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Catherine Stanton
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland
| | - Timothy G Dinan
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Psychiatry & Neurobehavioural Science, University College Cork, Cork, Ireland
| | - John F Cryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland.
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He L, Zeng L, Tian N, Li Y, He T, Tan D, Zhang Q, Tan Y. Optimization of food deprivation and sucrose preference test in SD rat model undergoing chronic unpredictable mild stress. Animal Model Exp Med 2020; 3:69-78. [PMID: 32318662 PMCID: PMC7167236 DOI: 10.1002/ame2.12107] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 03/05/2020] [Accepted: 03/06/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND The chronic unpredictable mild stress (CUMS) model has long been considered the best model for exploring the pathophysiological mechanisms underlying depression. However, there are no widely recognised standards for strategies for modeling and for behavioral testing. The present study aimed to optimize the protocols for food deprivation and the sucrose preference test (SPT) for the CUMS model. METHODS We first evaluated the effects of different long periods of food deprivation on the body weight of Sprague Dawley (SD) rats by testing food deprivation for 24 hours (8:00-8:00+), food deprivation for 12 hours during the daytime (8:00-20:00) and food deprivation for 12 hours at night (20:00-8:00+). Next, we established a SD rat CUMS model with 15 different stimulations, and used body weight measurement, SPT, forced swim test (FST), open field test (OFT) and Morris water maze (MWM) test to verify the success of the modeling. In the SPT, consumption of sucrose and pure water within 1 and 12 hours was measured. RESULTS Twelve hours of food deprivation during the daytime (8:00-20:00) had no effect on body weight, while 12 hours of food deprivation at night (20:00-8:00+) and 24 hours of food deprivation (8:00-8:00+) significantly reduced the mean body weight of the SD rats. When SPT was used to verify the successful establishment of the CUMS rat model, sucrose consumption measured within 12 hours was less variable than that measured within 1 hour. CONCLUSIONS Twelve hours of food deprivation in the daytime (8:00-20:00) may be considered a mild stimulus for the establishment of a CUMS rat model. Measuring sucrose consumption over 12 hours is recommended for SPT.
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Affiliation(s)
- Li‐Wen He
- Laboratory Animal CenterChongqing Medical UniversityChongqingChina
| | - Li Zeng
- Laboratory Animal CenterChongqing Medical UniversityChongqingChina
| | - Na Tian
- Pediatric Research InstituteChildren's Hospital of Chongqing Medical UniversityChongqingChina
| | - Yi Li
- Laboratory Animal CenterChongqing Medical UniversityChongqingChina
| | - Tong He
- Laboratory Animal CenterChongqing Medical UniversityChongqingChina
| | - Dong‐Mei Tan
- Laboratory Animal CenterChongqing Medical UniversityChongqingChina
| | - Qian Zhang
- Laboratory Animal CenterChongqing Medical UniversityChongqingChina
| | - Yi Tan
- Laboratory Animal CenterChongqing Medical UniversityChongqingChina
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Limanaqi F, Busceti CL, Biagioni F, Fornai F, Puglisi-Allegra S. Autophagy-Based Hypothesis on the Role of Brain Catecholamine Response During Stress. Front Psychiatry 2020; 11:569248. [PMID: 33093837 PMCID: PMC7527533 DOI: 10.3389/fpsyt.2020.569248] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 08/31/2020] [Indexed: 12/16/2022] Open
Abstract
Stressful events, similar to abused drugs, significantly affect the homeostatic balance of the catecholamine brain systems while activating compensation mechanisms to restore balance. In detail, norepinephrine (NE)- and dopamine (DA)-containing neurons within the locus coeruleus (LC) and ventral tegmental area (VTA), are readily and similarly activated by psychostimulants and stressful events involving neural processes related to perception, reward, cognitive evaluation, appraisal, and stress-dependent hormonal factors. Brain catecholamine response to stress results in time-dependent regulatory processes involving mesocorticolimbic circuits and networks, where LC-NE neurons respond more readily than VTA-DA neurons. LC-NE projections are dominant in controlling the forebrain DA-targeted areas, such as the nucleus accumbens (NAc) and medial pre-frontal cortex (mPFC). Heavy and persistent coping demand could lead to sustained LC-NE and VTA-DA neuronal activity, that, when persisting chronically, is supposed to alter LC-VTA synaptic connections. Increasing evidence has been provided indicating a role of autophagy in modulating DA neurotransmission and synaptic plasticity. This alters behavior, and emotional/cognitive experience in response to drug abuse and occasionally, to psychological stress. Thus, relevant information to address the role of stress and autophagy can be drawn from psychostimulants research. In the present mini-review we discuss the role of autophagy in brain catecholamine response to stress and its dysregulation. The findings here discussed suggest a crucial role of regulated autophagy in the response and adaptation of LC-NE and VTA-DA systems to stress.
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Affiliation(s)
- Fiona Limanaqi
- Department of Translational Research and New Technologies on Medicine and Surgery, University of Pisa, Pisa, Italy
| | | | | | - Francesco Fornai
- Department of Translational Research and New Technologies on Medicine and Surgery, University of Pisa, Pisa, Italy.,IRCCS Neuromed, Pozzilli, Italy
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Geng C, Qiao Y, Guo Y, Han W, Wu B, Wang C, Zhang J, Chen D, Yang M, Jiang P. Integrated metabolomics and lipidomics profiling of hippocampus reveal metabolite biomarkers in a rat model of chronic unpredictable mild stress-induced depression. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:781. [PMID: 32042797 DOI: 10.21037/atm.2019.11.21] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background Prolonged exposure to stress triggers depression, threatening human health. Thus, to thoroughly understand the underlying pathophysiologic mechanism of chronic unpredictable mild stress (CUMS)-induced depression is urgently needed. Ultra-high-performance liquid chromatography-mass spectroscopy (UPLC-MS)-based lipidomic and metabolomic approaches has been used for discovering metabolite biomarkers to develop new diagnostic and therapeutic means. Thus, our study aimed to conduct integrated metabolomics and lipidomics to identify metabolites and lipids biomarkers in the hippocampus in rat models of CUMS-induced depression. Methods Twelve eight-week-old male Sprague-Dawley rats (weight 210±30 g) were randomly distributed to one of the following two groups (n=6): control or CUMS. Established UPLC-MS-based lipidomic and metabolomic approaches were used to determine the metabolites and lipids in the hippocampus of rats. SICMA-P and GraphPad software were performed to discover potential metabolites and lipids biomarkers in the hippocampus of rats between the two groups. Results A total of 35 potential metabolites and 171 lipids were identified and found to be mainly related to amino acid and lipid metabolism. These metabolites were involved in different metabolic pathways and connected to each other, which might participate in the occurrence and development of depression. Conclusions Our findings underlined the metabolites, lipids and metabolic pathways that were changed in the hippocampus in CUMS compared to the controls, providing novel insights in the metabolism in the hippocampus of rats and revealing the new lipid-related targets.
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Affiliation(s)
- Chunmei Geng
- Institute of Clinical Pharmacy & Pharmacology, Jining First People's Hospital, Jining Medical University, Jining 272011, China
| | - Yi Qiao
- Department of Public Health, Jining Medical University, Jining 272011, China
| | - Yujin Guo
- Institute of Clinical Pharmacy & Pharmacology, Jining First People's Hospital, Jining Medical University, Jining 272011, China
| | - Wenxiu Han
- Institute of Clinical Pharmacy & Pharmacology, Jining First People's Hospital, Jining Medical University, Jining 272011, China
| | - Bin Wu
- Department of Gynecology, Taian City Central Hospital, Taian 271000, China
| | - Changshui Wang
- Institute of Clinical Pharmacy & Pharmacology, Jining First People's Hospital, Jining Medical University, Jining 272011, China
| | - Jun Zhang
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
| | - Dan Chen
- Institute of Clinical Pharmacy & Pharmacology, Jining First People's Hospital, Jining Medical University, Jining 272011, China
| | - Mengqi Yang
- Institute of Clinical Pharmacy & Pharmacology, Jining First People's Hospital, Jining Medical University, Jining 272011, China
| | - Pei Jiang
- Institute of Clinical Pharmacy & Pharmacology, Jining First People's Hospital, Jining Medical University, Jining 272011, China
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