Adolescent stress increases depression-like behaviors and alters the excitatory-inhibitory balance in aged mice

作     者：Hong-Li Wang Ya-Xin Sun Xiao Liu Han Wang Yu-Nu Ma Yun-Ai Su Ji-Tao Li Tian-Mei Si Wang Hong-Li;Sun Ya-Xin;Liu Xiao;Wang Han;Ma Yu-Nu;Su Yun-Ai;Li Ji-Tao;Si Tian-Mei

作者机构：National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital/Institute of Mental Health)and the Key Laboratory of Mental HealthMinistry of Health(Peking University)Beijing 100191China The Sixth People's Hospital of Hebei ProvinceBaodingHebei 071000China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2019年第132卷第14期

页      面：1689-1699页

核心收录：

学科分类：1002[医学-临床医学] 10[医学] 

基　　金：grants from the National Natural Science Foundation of China (Nos. 81630031, 81401129, 81571321, and 81571312) the Beijing Brain Project (No.Z171100000117016), the National Key Basic Research Program of China (973 program No. 2015CB856401) the Peking University Medicine Seed Fund for Interdisciplinary Research (No. BMU2017MX021). 

主　　题：Adolescence Aging Depression Inter-neuron Stress Vesicular glutamate transporter-1 

摘      要：Background:Depression affects approximately 5% of elderly people and its etiology might be related to chronic stress exposure during neurodevelopmental periods.In this study,we examined the effects of adolescent chronic social stress in aged mice on depressive behaviors and the excitatory-inhibitory (E/I) balance in stress-sensitive regions of the brain.Methods:Sixty-four adolescent,male C57BL/6 mice were randomly assigned to either the 7-week (from post-natal days 29 to 77) social instability stress (stress group,n =32) or normal housing conditions (control group,n =32).At 15 months of age,16 mice were randomly selected from each group for a series of behavioral tests,including two depression-related tasks (the sucrose preference test and the tail suspension test).Three days following the last behavioral test,eight mice were randomly selected from each group for immunohistochemical analyses to measure the cell density of parvalbumin (PV+)-and calretinin (CR+)-positive gamma-aminobutyric-acid (GABA)ergic inhibitory inter-neurons,and the expression levels of vesicular transporters of glutamate-1 (VGIuT1) and vesicular GABA transporter (VGAT) in three stress-sensitive regions of the brain (the medial pre-frontal cortex [mPFC],hippocampus,and amygdala).Results:Behaviorally,compared with the control group,adolescent chronic stress increased depression-like behaviors as shown in decreased sucrose preference (54.96 ± 1.97% vs.43.11 ± 2.85%,t(22)=3.417,P =0.003) and reduced latency to immobility in the tail suspension test (92.77 ± 25.08 s vs.33.14 ± 5.95 s,t(25)=2.394,P =0.025),but did not affect anxiety-like behaviors and pre-pulse inhibition.At the neurobiologic level,adolescent stress down-regulated PV+,not CR+,inter-neuron density in the mPFC (F(1,39)=19.30,P 10.09,all P 0.004),which suggests stress-induced hypoexcitability in these regions.Conclusions:Chronic stress during adolescence increased depression-like behaviors in aged mice,which may be associated with the F/I imbalance in stress-sensitive brain regions.