摘要
近年来,随着神经科学与分子生物学技术的革新性发展,应激相关精神疾病的生物学机制研究取得重要突破.然而,应激相关精神疾病高度复杂的病理过程及个体异质性特征,仍是当前亟需深入探索的科学前沿问题.本文首先从模式动物的选择与构建及评估方法入手,阐述了基于应激源和生物学机制两方面构建的动物模型.在此基础上分析了大脑与外周系统之间的双向调节机制,这种互作主要通过神经-内分泌-免疫网络、“体-脑”轴等多途径影响疾病的发生发展.基于个体差异的应激易感性、心理韧性和性别差异的机制研究,为应激相关精神疾病的干预提供了新的方向.此外,反转化研究利用已有药物的再研究和大数据驱动的研究范式,使得应激相关精神疾病的机制研究更加高效.综上,脑体互作及个体差异的机制研究,结合反转化研究范式,为应激相关精神疾病的生物机制研究提供新的机遇.
In parallel with paradigm-shifting advances in neuroscience and molecular biological methodologies,while significant strides have been made in delineating the biological mechanisms underlying stress-related mental disorders,the multifaceted pathophysiological processes and substantial individual heterogeneity remain critical frontiers warranting comprehensive scientific investigation.This review initially focuses on the selection,establishment,and evaluation methodology of animal models,delineating the construction of experimental models based on both stress factors and underlying biological mechanisms.Building upon this foundation,this paper examines the bidirectional regulatory mechanisms between central and peripheral systems,which predominantly function through major pathways encompassing the neuro-endocrine-immune network,“body-brain"axis,and multiple stress-mediated pathological progressions.Mechanistic elucidation of psychological resilience and sex-specific differences based on individual differences provides novel therapeutic paradigms for stress-related mental disorders.Additionally,reverse translation research methodology integrates established pharmacological findings and big data-driven analytical paradigms to enhance the efficiency and precision of mechanistic investigations in stress-related mental disorders.In conclusion,the mechanistic investigations of brain-body interactions and individual heterogeneity,combined with reverse translation approaches,may illuminate novel pathways for understanding the biological mechanisms underlying stress-related mental disorders.
作者
史栋栋
王立平
李晓明
胡霁
秦绍正
赵敏
段树民
王以政
王振
SHI DongDong;WANG LiPing;LI Xiao-Ming;HU Ji;QIN ShaoZheng;ZHAO Min;DUAN ShuMin;WANG YiZheng;WANG Zhen(Shanghai Mental Healh Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200030,China;The Brain Cognition and Brain Disease Institute,Shenzhen Institute ofAdvanced Technology,Chinese Academy of Sciences.Shenzhen 518055,China;Deparment of Neurologyof Second Afiliated Hospital and Schoolof Brain Science and Brain Medicine,Zhejiang University Schoolof Medicine,Hangzhou 310063,China;Laboratory of Stress Neurobiology School of Life Science and Technology,ShanghaiTech University,Shanghai 201210,China;State Key Laboratory of Cognitive Neuroscience and Learning&IDG/MeGovern Institute for Brain Research,Bejing Normal University Beijing 100875,China.;School of Brain Science and Brain Medicine,Zhejiang University School of Medicine,Hangzhou 310063,China;Institute for Translational Brain Research,Fudan University,Shanghai 200032,China)
出处
《中国科学:生命科学》
北大核心
2025年第7期1361-1372,共12页
Scientia Sinica(Vitae)
关键词
应激
精神疾病
脑体互作
应激易感性
心理韧性
性别差异
stress
mental disorders
brain-body interactions
stress susceptibility
resilience
sex-specific differences
