压力应激韧性的神经机制  

The neural mechanisms of resilience

作　　者：严晶晶 曹罡 王崇元 孙毅 韩明虎 Jingjing Yan;Gang Cao;Chongyuan Wang;Yi Eve Sun;Minghu Han(Brain Cognition and Brain Disease Institute,Shenzhen Institute of Advanced Technology(SIAT),Chinese Academy of Sciences,Shenzhen 518055,China;Department of Mental Health and Public Health,Faculty of Life and Health Sciences,Shenzhen Institute of Advanced Technology(SIAT),Chinese Academy of Sciences,Shenzhen 518055,China;Department of Biology,Faculty of Life and Health Sciences,Shenzhen Institutes of Advanced Technology(SIAT),Chinese Academy of Sciences,Shenzhen 518055,China;Faculty of Pharmaceutical Sciences,Shenzhen Institutes of Advanced Technology,Chinese Academy of Science,Shenzhen 518055,China)

机构地区：[1]中国科学院深圳先进技术研究院脑认知与脑疾病研究所,深圳518055 [2]深圳理工大学生命健康学院精神健康与公共卫生系,深圳518055 [3]深圳理工大学生命健康学院生物系,深圳518055 [4]深圳理工大学药学院,深圳518055

出　　处：《科学通报》2023年第35期4807-4820,共14页Chinese Science Bulletin

基　　金：科技创新2030-“脑科学与类脑研究”重大项目(2021ZD0202902);国家自然科学基金外国学者研究基金(T2250710685);深圳市基础研究专项(深圳市自然科学基金)重点项目(JCYJ20220818101600001);深圳市抑郁障碍精准诊疗重点实验室(ZDSYS20220606100606014)资助。

摘　　要：抑郁症是最常见的精神疾病之一,其患病人群在不断增长.并且,抑郁症的终生患病率为15%~18%,即大约每5人中就有一个人在其一生中经历过抑郁发作.压力应激作为一种环境因素是抑郁症的主要成因之一.经历了压力应激却没有发展至抑郁症的人群具有压力应激韧性(resilience).探索压力应激韧性的神经机制,对抑郁症在临床上预防和治疗将发挥至关重要的作用.本文主要关注压力应激韧性的神经机制的研究进展,首先简要介绍了压力应激韧性研究中常用的慢性社交挫败应激模型(chronic social defeat stress,CSDS),其次重点对压力应激韧性相关的大脑区域在分子、细胞和神经环路水平上的研究进展进行总结,接下来介绍压力应激韧性的临床前机制研究所带来的临床转化,最后讨论和展望压力应激韧性在未来的研究方向.Major depressive disorder(MDD)is one of the most common neuropsychiatric disorders,affecting approximately 280 million people worldwide.Furthermore,the lifetime prevalence of MDD is approximately 20%.Individuals suffering from MDD are unable to experience a normal life and often have suicide ideation,which becomes a major threat to themselves and significant burden to their families and society.Moreover,the development of new therapeutic drugs is lagging behind.Roughly 50%of patients with depression fail to respond to first-line antidepressant therapy.Thus,it is essential to identify innovative therapeutic targets based on research into the etiology and pathology of depression.Stress,as an environmental risk factor,is a major cause of depression.Compared to the individuals who are sensitive to stress and prone to develop depression(susceptible),most individuals are capable of adapting well and being resilient to avoid depression(resilient).As a result,studying the mechanism of resilience provides a new avenue for finding new treatment strategies.Indeed,resilience to depression has attracted an increasing number of researchers,leading to significant advances in understanding resilience mechanisms.The main purpose of this review article is to summarize the development of resilience investigations in four parts.The first is an introduction to the chronic social defeat stress(CSDS)model,which has been widely used in research on stress resilience in rodents.Depressive-like behaviors such as social avoidance and anhedonia can be induced by CSDS.And chronic treatment of typical antidepressants and acute treatment of ketamine normalize these aberrant behaviors seen in CSDS model.The model is also used to segregate the socially defeated animals into susceptible and resilient subgroups.Second,we show how the brain nuclei involved in stress resilience influence resilient phenotype at the molecular,cellular and circuit levels.These brain regions are mainly the ventral tegmental area(VTA),nucleus accumbens(NAc),locus coeruleu

关 键 词：抑郁症 应激韧性 慢性社交挫败应激模型 中脑腹侧被盖区 伏隔核 蓝斑 

分 类 号：R749.4[医药卫生—神经病学与精神病学]