氧化应激影响中枢谷氨酸神经递质系统诱发抑郁症  

Oxidative Stress Induces Depression by Altering Central Glutamate Neurotransmission

作　　者：张薇 李传玉 张波 ZHANG Wei;LI Chuan-Yu;ZHANG Bo(Guangxi Key Laboratory of brain and cognitive neuroscience,Faculty of Basic Medical Sciences,Guilin Medical University,Guilin 541199,Guangxi,China)

机构地区：[1]桂林医学院基础医学院广西脑与认知神经科学重点实验室,广西桂林541199

出　　处：《中国生物化学与分子生物学报》2024年第10期1352-1361,共10页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No.32260200);广西壮族自治区自然科学基金(No.2020GXNSFAA297134);广西科技基地和人才专项(No.AD20238023)资助。

摘　　要：抑郁症广泛且严重影响人类身心健康,其核心症状为抑郁心境和快感缺失。临床和动物研究陆续揭示抑郁症复杂致病机制,其中大脑单胺类递质缺陷机制极大促进了临床一线抗抑郁药物研发应用。单胺类抗抑郁药物起效需持续用药2周以上,对约1/3抑郁患者无显著疗效。氯胺酮类药物以中枢谷氨酸递质系统为主要作用靶点,具有快速且持久抗抑郁效果,但此类药物有潜在成瘾和致幻副作用,因此,仅被美国食品药品监督管理局批准用于难治性和有严重自杀倾向的重度抑郁患者。寻找能快速起效但副作用小的抗抑郁药物,是当前疾病治疗的重点方向,而深入揭示抑郁症复杂致病机制则是前提。近年研究发现,氧化应激是抑郁症重要致病机制,而运动和复合膳食等天然抗氧化方式能有效缓解抑郁症状,是值得探索的抗抑郁途径。本文综述了中枢谷氨酸系统功能异常与抑郁症密切的关系,以及氧化应激对谷氨酸系统的影响和相关分子机制,旨在为疾病预防治疗提供新思路和药物靶点。Depression,a category of mental disorder characterized by core symptoms of anhedonia and depressed mood,seriously influences the physical and psychological health of people worldwide.Clinical and animal studies have been gradually revealing the complicated pathogenic mechanisms involved,and have proposed related hypothesis.The monoamine neurotransmitter deficiency theory has significantly contributed to the development and clinical application of the first-line antidepressants,however,the monoamine targeted drugs generally require more than two weeks of continuous drug treatment,and moreover,are ineffective for approximately one-third of depressed patients.Esketamine is a kind of rapid-acting antidepressant mainly targeting the central glutamatergic system,which is only approved by Food and Drug Administration for treating treatment-resistant depression and major depressive patients with severe suicidal tendency,owing to its potential addictive and psychotomimetic side effects.The search for antidepressants that can rapidly produce effects with minimal side effects remains a key direction for disease treatment,and this endeavor necessitates a deeper understanding of the complex pathogenesis underlying the disease.Recent studies have revealed oxidative stress as a crucial factor in the pathogenesis of depression,and natural antioxidant methods such as exercise and composite dietary can effectively alleviate depressive symptoms,which could serve as promising therapeutic antidepressant approaches.Therefore,we review the close relationship between central glutamatergic system and depression onset,the influence of oxidative stress on glutamate neurotransmission,and the underlying molecular mechanisms involved,to provide novel ideas and drug targets for the prevention and treatment of the disease.

关 键 词：抑郁症 氧化应激 谷氨酸兴奋毒性 

分 类 号：R749[医药卫生—神经病学与精神病学]