MOLECULAR NEUROBIOLOGY
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2024
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IF 4.6
Guo Lin,Liu Ziyu,Jia Xiaoxia,Wang Qinghua,Ji Jianlun,Lv Na,Liu Zhidong,Zhou Qin,Sun Congcong,Wang Yun
Several lines of evidence have highlighted the crucial role of mitochondria-based therapy in depression. However, there are still less mitochondrial targets for the depression treatment. TAM41 mitochondrial translocator assembly and maintenance homolog (TAMM41) is a mitochondrial inner membrane protein for maintaining mitochondrial function, which is tightly related to many brain diseases including Alzheimer’s diseases and epilepsy. Here, we investigated whether TAMM41 would be a potential target to treat depression. We found that the expression of TAMM41 was markedly lower in corticosterone-induced depression, lipopolysaccharide-induced depression, and depressed patients. Meanwhile, loss of TAMM41 resulted in increased immobility in the forced swim test (FST), tail suspension test (TST), and center time in open field test (OFT), suggesting depressive-like behaviors in mice. Moreover, genetic overexpression of TAMM41 obviously exerted antidepressant-like activities. Mechanistically, proteomics revealed that pacsin1 might be the underlying target of TAMM41. Further data supported that TAMM41 regulated the expression of pacsin1, and its antidepressant-like effect at least partially was attributed to pacsin1. In addition, exosomes containing TAMM41 was sufficient to exhibit antidepressant-like effect, suggesting an alternative strategy to exert the effect of TAMM41. Taken together, the present study demonstrates the antidepressant-like effect of TAMM41 and sheds light on its molecular mechanism. These finding provide new insights into a therapeutic strategy targeting mitochondria in the development of novel antidepressants.
研究领域:
神经科学
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分子生物学
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药理学
✓ 已验证
DOI
高影响因子
Frontiers in Psychiatry
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2021
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IF 4.157
Jiang Ning,Wang Haixia,Huang Hong,Lv Jingwei,Zeng Guirong,Wang Qiong,Bao Yu,Chen Ying,Liu Xinmin
Depression is a common yet severe neuropsychiatric condition that causes imposes considerable personal, economic, and social burdens worldwide. Medicinal plant species (e.g., Panax ginseng and Polygala tenuifolia) demonstrate potent antidepressant-like effects with less toxicity and other side effects. Shen yuan prescription (SY), composed of Panax ginseng (GT) and Polygala tenuifolia (YT). The present study aimed to elucidate the effects of SY treatment on chronic unpredictable mild stress (CUMS) rats and study the underlying mechanism. Our results indicated that SY (67.5, 135, or 270 mg/kg) significantly reverses the depressive-like behaviors in rats with a 5-week CUMS exposure, as demonstrated by increased sucrose consumption in the sucrose preference test, and decreased immobility time in the tail suspension and forced swim test. Moreover, SY altered serum corticosterone levels, pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), and oxidative markers (SOD, CAT, and MDA), and increased the levels of hippocampal neurotransmitters (5-HT, DA, and NE) in rats exposed to CUMS. Furthermore, rats treated with SY showed a reduction in the protein expression of BDNF, p-TrkB, p-Akt, and p-mTOR proteins induced by CUMS exposure in the hippocampus. In conclusion, SY prevented depressive-like behaviors in CUMS-exposed rats by preventing hypothalamus-pituitary-adrenal axis dysfunction, decreasing the levels of the neurotransmitters, minimizing oxidative stress, suppressing neuroinflammation, and activating the PI3K/Akt/mTOR-mediated BDNF/TrkB pathway, all of which are the key players in the pathological basis of depression.
研究领域:
神经精神病学
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药理学
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行为神经科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2018
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IF 3.457
Yu Wang,Shanshan Zhao,Xu Liu,Yumin Zheng,Lei Li,Su Meng
Objective Autism is a neurodevelopmental disorder which significantly impacts the quality of people’s life. Oxytocin is a hormone impacting the social cognition and interpersonal trust. In this study, we aimed to explore the role of oxytocin in autism. Methods Autistic mice models were established by valproate . Animal behaviors were assessed by open field test, tail suspension test , marble burying test and three-chamber social interaction test. Oxidative stress was evaluated by the levels or activities of malondialdehyde , superoxide dismutase , glutathion peroxidase , reduced glutathione and reactive oxygen species . Inflammation was assessed by the levels of tumor necrosis factor-α, interleukin-1β and interleukin-6. The number of activated microglia was detected by immunofluorescence with an Iba-1 antibody. Results Our results showed that oxytocin improved the behaviors of autistic mice, with less anxiety, depression and repetitive behavior , and ameliorated social interaction. Further study showed that the elevated oxidative stress and inflammation in autistic mice were alleviated after treatment of oxytocin. Conclusion Our study demonstrates that oxytocin treatment ameliorates autism in a mouse model, maybe through its modulation on oxidative stress and inflammation. It is indicated that oxytocin may beneficial to autism.
研究领域:
神经科学
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药理学
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行为科学
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
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