运动改善ASMT基因敲除小鼠抑郁行为的海马蛋白质组学机制  

Hippocampal Proteomic Mechanisms of Exercise Alleviating Depressive-like Behaviors in ASMT Knockout Mice

作　　者：章森 刘文彬[1,2] 夏杰 李玲侠[1,2] 黄卓淳[1,2] 邹勇 漆正堂 刘微娜[1,2] ZHANG Sen;LIU Wenbin;XIA Jie;LI Lingxia;HUANG Zhuochun;ZOU Yong;QI Zhengtang;LIU Weina(Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education,East China Normal University,Shanghai 200241,China;School of Physical Education and Health,East China Normal University,Shanghai 200241,China)

机构地区：[1]华东师范大学青少年健康评价与运动干预教育部重点实验室,上海200241 [2]华东师范大学体育与健康学院,上海200241

出　　处：《上海体育大学学报》2024年第3期36-48,共13页Journal of Shanghai University of Sport

基　　金：国家自然科学基金面上项目(32271174);国家自然科学基金面上项目(31871208)。

摘　　要：目的利用定量蛋白质组学技术探究N-乙酰基-5-羟色胺-甲基转移酶(N-acetyl-5-hydroxytryptamine-methyltransferase,ASMT)基因敲除及运动干预对小鼠抑郁行为及海马蛋白质组的影响。方法将雄性ASMT基因敲除小鼠及野生型小鼠随机分为安静组和运动组。5周的游泳运动干预结束后全部进行抑郁行为学检测。行为学结束后进行麻醉处死取海马组织。采用TMT标记定量蛋白质组学技术检测海马组织中的蛋白表达情况,并运用生物信息学方法分析。结果ASMT基因敲除后小鼠具有显著的抑郁行为表型,游泳运动干预后可以显著改善。筛选出的差异蛋白功能集中在突触信号通路、突触化学传递的调控、突触囊泡循环、神经发生、神经系统发育的调控、长时程突触增强、SNARE复合体聚集等。结论ASMT基因敲除可能会通过海马突触前膜的SNARE家族蛋白过度表达诱导谷氨酸的过度释放并产生神经毒性,进而产生抑郁行为;游泳运动可能通过调节突触转运相关蛋白SNAP25维持神经递质稳态,促进神经发生水平和突触可塑性,进而使ASMT基因敲除小鼠抑郁行为得到改善。Objective N-acetyl-5-hydroxytryptamine-methyltransferase(ASMT)is the rate-limiting enzyme for melatonin synthesis and has physiological significance in the regulation of circadian rhythms and mental health.Methods Male ASMT knockout mice and wild-type mice were randomly divided into sedentary and exercise groups. All were tested for depression behaviorally at the end of the five-week swimming exercise intervention. Anesthetic execution was performed to remove the hippocampal tissue at the end of the behavioral study. Quantitative proteomics techniques were used to detect protein expression in hippocampal tissues and bioinformatics methods were applied for differential protein screening and enrichment pathway analysis. Results It was found that ASMT knockout mice had a significant depressive-like behavioral phenotype that was significantly improved by swimming exercise intervention. TMT-based quantitative proteomics screened for differential protein functions focused on synaptic signaling pathways, regulation of synaptic chemotransmission, vesicle localization, vesicle-regulated transport at synapses, synaptic vesicle recycling, neurogenesis, regulation of nervous system development, long-term potentiation, and SNARE complex aggregation, etc. Conclusions The depressive behavior of ASMT knockout mice was associated with abnormal hippocampal synaptic protein expression, which in turn affected the neurotransmitter transmission, synaptic membrane fusion and other functions of hippocampal neurons, and affected synaptic plasticity of hippocampal neurons through signaling pathways such as synaptic vesicle recycling pathway, glutamatergic synaptic pathway, and long-term potentiation. The improvement of depressive- like behaviors in ASMT knockout mice by swimming exercise affects hippocampal neuronal neurogenesis and neuronal differentiation through synaptic vesicle recycling pathway.

关 键 词：N-乙酰基-5-羟色胺-甲基转移酶 游泳运动 抑郁行为 海马 蛋白质组学 

分 类 号：R749.4[医药卫生—神经病学与精神病学] G804.2[医药卫生—临床医学]