首页|丰富环境对抑郁样小鼠行为及海马锥体神经元突触传递的影响

丰富环境对抑郁样小鼠行为及海马锥体神经元突触传递的影响

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目的 探讨丰富环境对慢性应激所致抑郁样小鼠行为及海马锥体神经元突触传递功能的影响.方法36只7周龄SPF级雄性C57BU6J小鼠按照随机区组法分为对照组、模型组、丰富环境组,每组12只.模型组和丰富环境组小鼠采用慢性不可预知性温和应激方法建立抑郁模型,造模期间丰富环境组小鼠每天在丰富环境中生活6 h,其余时间与对照组、模型组小鼠均生活在常规环境中.采用糖水偏爱实验、悬尾实验、强迫游泳实验检测小鼠抑郁行为,采用旷场实验检测小鼠运动能力及焦虑行为,采用Morris水迷宫实验检测小鼠认知功能.采用离体电生理技术记录海马场兴奋性突触后电位(field excitatory post-synaptic potentials,fEPSP),采用全细胞记录检测海马锥体神经元自发性兴奋性突触后电流(spontaneous excitatory post-synaptic currents,sEPSC)及微小兴奋性突触后电流(miniature excitatory post-synaptic currents,mEPSC).采用 SPSS 23.0 软件进行统计分析,多组间比较采用单因素方差分析和重复测量方差分析.结果(1)行为学结果显示:3组小鼠在旷场中央区的活动总时间、糖水偏爱率、悬尾和强迫游泳不动时间均差异有统计学意义(F=17.12,26.07,41.13,60.18,均P<0.01).模型组小鼠中央区活动时间、糖水偏爱率均低于对照组(均P<0.01),悬尾不动时间和强迫游泳不动时间均高于对照组(均P<0.01);丰富环境组小鼠中央区活动时间[(56.56±3.47)s]、糖水偏爱率[(71.22±8.37)%]均高于模型组[(52.56±3.47)s,(59.53±8.72)%](均P<0.05),悬尾不动时间[(94.19±10.77)s]和强迫游泳不动时间[(76.98±12.10)s]均低于模型组[(104.58±8.24)s,(111.41±9.56)s](均P<0.05).(2)空间学习记忆力结果表明,3组小鼠寻找平台潜伏期的组别与时间交互效应显著(F=12.02,P<0.01);模型组小鼠寻找平台的潜伏期均高于对照组和丰富环境组(均P<0.01).空间探索结果表明,3组小鼠目标象限停留时间与穿越平台次数均差异有统计学意义(F=19.67,20.27,均P<0.01);模型组小鼠目标象限停留时间和穿越平台次数均低于对照组和丰富环境组(均P<0.01).(3)电生理实验结果表明,3组小鼠fEPSP的组别与刺激强度交互效应显著(F=1.86,P<0.01),在150 mA和200 mA刺激强度时,模型组小鼠的fEPSP均低于对照组和丰富环境组(均P<0.05).(4)长时程增强(long-term potentiation,LTP)结果表明,3组小鼠的LTP差异有统计学意义(F=15.32,P<0.01),模型组小鼠的LTP[(137.42±4.48)%]低于对照组[(156.62±4.79)%]和丰富环境组[(147.86±9.14)%](均P<0.05).(5)全细胞记录结果表明,3组小鼠sEPSC、mEPSC频率均差异有统计学意义(F=15.30,13.72,均P<0.01),模型组小鼠的sEPSC、mEPSC 频率[(0.60±0.31)Hz,(0.63±0.26)Hz]均低于对照组[(1.27±0.46)Hz,(1.02±0.28)Hz]和丰富环境组[(0.96±0.45)Hz,(0.83±0.22)Hz](均P<0.05).结论 丰富环境能够改善慢性应激所致小鼠的抑郁行为,并能够提高抑郁小鼠的认知能力,增强海马锥体神经元突触传递及突触可塑性.
Effects of enriched environment on behavior and synaptic transmission in hippocampal pyramidal neurons of depressive-like mice
Objective To investigate the effects of enriched environment on the behavior of depres-sive-like mice induced by chronic stress and the synaptic transmission function of hippocampal pyramidal neurons.Methods Thirty-six 7-week-old SPF grade male C57BL/6J mice were divided into control group,model group and enriched environment group according to the random zone method,with 12 mice in each group.The mice in model group and enriched environment group were subjected to chronic unpredictable mild stress to establish depression models.During the modeling period,the mice in enriched environment group lived in the enriched environment for 6 hours per day,and lived in the routine environment for the rest time just like the mice in control group and model group.The depressive behaviors of mice were detected by sucrose preference test(SPT),forced swimming test(FST)and tail suspension test(TST).The motor func-tion and anxious behavior of mice were detected by open field test(OFT)and the cognitive function was de-tected by Morris water maze test.In vitro electrophysiological techniques were used to record field excitatory post-synaptic potentials(fEPSP)in the hippocampus,and whole-cell recording was used to record spontane-ous excitatory post-synaptic currents(sEPSC)and miniature excitatory post-synaptic currents(mEPSC)in hippocampal pyramidal neurons.Statistical analysis was conducted by SPSS 23.0 software.Multiple group comparisons of data were conducted by one-way ANOVA and repeated measures ANOVA.Results(1)Be-havioral results showed statistically significant differences among the three groups in terms of total activity time in the central area of OFT,sugar water preference rate of SPT and immobility time of TST and FST(F=17.12,26.07,41.13,60.18,all P<0.01).The activity time in the central area of OFT and sugar water pref-erence rate of model group were lower than those in the control group(both P<0.01),and the immobility time of TST and FST were higher than those in the control group(both P<0.01).The activity time in the central area of OFT((56.56±3.47)s)and sugar water preference rate((71.22±8.37)%)of enriched environment group were higher than those in the model group((52.56±3.47)s,(59.53±8.72)%)(all P<0.05),and the immobility time of TST((94.19±10.77)s)and FST((76.98±12.10)s)were lower than those in the model group((104.58±8.24)s,(111.41±9.56)s)(all P<0.05).(2)The results of spatial learning memory showed that there was a significant difference of group and time interaction effects for laten-cy to find the platform(F=12.02,P<0.01),and the latency to find the platform in model group was higher than that in control group and enriched environment group(both P<0.01).The results of spatial exploration showed that there were statistically significant differences in the target quadrant residence time and the times crossing the platform among the three groups(F=19.67,20.27,both P<0.01).The both indexes in the mod-el group were lower than those in control group and enriched environment group(all P<0.01).(3)The re-sults of electrophysiological experiment showed that the interaction effect of fEPSP between groups and stimu-lations intensity among the three groups was significant(F=1.86,P<0.01).At the stimulation level of 150 mA and 200 mA,the fEPSP of the model group was lower than those of control group and enriched envi-ronment group(all P<0.05).(4)The results of the long-term potentiation(LTP)showed a statistically sig-nificant difference among the three groups(F=15.32,P<0.01).The LTP of the model group mice((137.42±4.48)%)was lower than those of the control group((156.62±4.79)%)and the enriched en-vironment group((147.86±9.14)%)(both P<0.05).(5)The whole-cell recordings results showed that there was a statistically significant difference in the frequencies of sEPSC and mEPSC among the three groups(F=15.30,13.72,both P<0.01).The sEPSC and mEPSC frequencies of the model group mice((0.60±0.31)Hz,(0.63±0.26)Hz)were lower than those of the control group((1.27±0.46)Hz,(1.02±0.28)Hz)and the enriched environment group((0.96±0.45)Hz,(0.83±0.22)Hz)(all P<0.05).Conclusion Environmental enrichment can alleviate the depressive behaviors induced by chronic stress and enhance cognitive performance,hipp-ocampal pyramidal neuron synaptic transmission and synaptic plasticity in depressive-like mice.

Enriched environmentChronic stressDepressionHippocampusSynaptic plasticityExcitatory post-synaptic potentialExcitatory post-synaptic currentMouse

陈进东、朱传安、马增明、夏玉平

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福建医科大学临床医学院,福州 350122

厦门市仙岳医院,厦门医学院附属仙岳医院,福建省精神医学中心,福建省精神疾病临床医学研究中心,厦门 361012

丰富环境 慢性应激 抑郁 海马 突触可塑性 兴奋性突触后电位 兴奋性突触后电流 小鼠

福建省2022年省级临床重点专科建设项目福建省卫生健康科技计划项目福建省科技计划项目厦门市医疗卫生指导性项目

闽卫医政函[2022]884号2021QNB0262022D0083502Z20214ZD1278

2024

中华行为医学与脑科学杂志
中华医学会 济宁医学院

中华行为医学与脑科学杂志

CSTPCD北大核心
影响因子:1.472
ISSN:1674-6554
年,卷(期):2024.33(9)