丰富环境通过上调海马LASP1改善父系应激致子代小鼠焦虑抑郁样行为  

Environmental enrichment ameliorates anxiety and depression-like behaviors in paternally stressed offspring mice through upregulation of hippocampal LASP1

作　　者：王雪琴 王来法 张辉 邓玲 崔艳慧 WANG Xueqin;WANG Laifa;ZHANG Hui;DENG Ling;CUI Yanhui(Center for Neuroscience and Behavior,Academician Workstation,Changsha Medical University,Changsha 410219;Department of Anatomy and Neurobiology,School of Basic Medical Science,Central South University,Changsha 410013,China)

机构地区：[1]长沙医学院院士工作站神经科学与行为学研究中心,湖南长沙410219 [2]中南大学基础医学院人体解剖学与神经生物学系,湖南长沙410013

出　　处：《西安交通大学学报（医学版）》2023年第4期542-548,共7页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：湖南省自然科学基金资助项目(No.2020JJ5627);湖南省教育厅科学研究项目(No.19B069)资助

摘　　要：目的探索丰富环境(environmental enrichment,EE)在父系应激致子代焦虑、抑郁样行为中的作用及其可能机制。方法给予雄性C57BL/6小鼠(F0)慢性温和不可预知应激(unpredictable chronic mild stress,UCMS),随后与正常雌鼠交配获得F1子代(F1-UCMS)小鼠。在F1-UCMS子代小鼠幼年期(3~5周龄)分别给予标准环境(standard environment,SE)和丰富环境(EE)干预,成年后(8周龄)采用旷场实验(open field test,OFT)、高架十字迷宫实验(elevated plus-maze test,EPM)检测小鼠焦虑样行为,采用强迫游泳实验(forced swimming test,FST)、糖水偏好实验(sucrose preference test,SPT)检测小鼠抑郁样行为。通过实时荧光定量PCR(Real-time fluorescence quantitative PCR,RT-qPCR)和蛋白免疫印迹(Western blotting)检测成年F1-UCMS小鼠海马LIM和SH3结构域蛋白1(LIM and SH3 domain protein 1,LASP1)的表达。结果与正常父系的F1子代(F1-Nor)相比,应激父系的F1子代F1-UCMS小鼠在OFT的中央区域停留时间百分比减少、EPM的开放臂停留时间百分比减少(P均<0.05),表现出明显焦虑样行为;F1-UCMS组小鼠在FST的不动时间百分比增加、SPT的糖水消耗百分比减少(P均<0.01),表现出明显抑郁样行为。与SE组相比,EE组小鼠在OFT的中央区域停留时间百分比增加[雄性:(7.44±0.75)%vs.(14.93±1.74)%,P<0.01;雌性:(8.89±1.06)%vs.(15.10±1.82)%,P<0.05]、EPM的开放臂停留时间百分比增加[雄性:(8.09±1.05)%vs.(14.15±1.88)%,P<0.05;雌性:(9.13±1.14)%vs.(14.04±1.37)%,P<0.05],表明EE改善父系应激导致的F1-UCMS小鼠焦虑样行为;EE组小鼠在FST的不动时间百分比减少[雄性:(58.63±4.51)%vs.(42.15±3.81)%,P<0.05;雌性:(57.96±4.19)%vs.(43.25±4.22)%,P<0.05]、SPT的糖水消耗百分比增加[雄性:(50.38±3.47)%vs.(70.39±3.12)%,P<0.01;雌性:(52.42±2.84)%vs.(69.99±3.55)%,P<0.01],表明EE改善父系应激导致的F1-UCMS小鼠抑郁样行为。RT-qPCR及Western blotting检测结果显示,与F1-Nor组相比,SE组子代小鼠海马LObjective To explore the role of environmental enrichment(EE)in paternal stress-induced anxiety and depression-like behaviors in offspring and its potential mechanisms.Methods Male C57BL/6 mice(F0)were treated with unpredictable chronic mild stress(UCMS)and subsequently mated with normal females to obtain F1 offspring mice.The standard environment(SE)and enriched environment(EE)were administered to F1-UCMS offspring mice during their early life(3-5 weeks of age).Anxiety-like behaviors were detected by open field test(OFT)and elevated plus-maze test(EPM);depression-like behaviors were detected via forced swimming test(FST)and sucrose preference test(SPT)at the age of 8 weeks.The expressions of LIM and SH3 domain protein 1(LASP1)in the hippocampus of adult F1 offspring mice were detected by Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting.Results Compared to F1 offspring of normal paternal(F1-Nor),F1 offspring mice of the stressed paternal(F1-UCMS)showed significantly anxiety-like behavior with reduced percentage of time spent in the central region of OFT and in the open arm of EPM(P<0.05);mice from the F1-UCMS group showed a significantly increased percentage of immobility in FST and a reduced percentage of sugar consumption in SPT(P<0.01),which demonstrated significant depression-like behaviors.Compared to the SE group,mice in the EE group had an increased percentage of time spent in the central region of the OFT[males:(7.44±0.75)%vs.(14.93±1.74)%,P<0.01;females:(8.89±1.06)%vs.(15.10±1.82)%,P<0.05]and an increased percentage of time in the open arm of EPM[males:(8.09±1.05)%vs.(14.15±1.88)%,P<0.05;females:(9.13±1.14)%vs.(14.04±1.37)%,P<0.05].This indicated that EE ameliorated anxiety-like behavior in F1-UCMS mice with paternal stress.Compared to the SE group,mice in the EE group had an decreased percentage of immobility in FST[males:(58.63±4.51)%vs.(42.15±3.81)%,P<0.05;females:(57.96±4.19)%vs.(43.25±4.22)%,P<0.05]and an increased percentage of sugar consumption in SPT[males:(50.38±

关 键 词：丰富环境 焦虑 抑郁 慢性温和不可预知应激(UCMS) LASP1 

分 类 号：R74[医药卫生—神经病学与精神病学]