早期睡眠剥夺对成年抑郁模型小鼠行为及海马突触可塑性的影响  

Effects of early sleep deprivation on depressive-like behavior and hippocampus synaptic plasticity in adult depression model mice

作　　者：焦清艳[1] 孙芸[1] 曹海燕 张新军[1] 纪丽杰 张家瑞 李洁 Jiao Qingyan;Sun Yun;Cao Haiyan;Zhang Xinjun;Ji Lijie;Zhang Jiarui;Li Jie(Department of Sleep,Tianjin Anding Hospital,Tianjin 300222,China;Department of Child and Adolescent Psychology,Tianjin Anding Hospital,Tianjin 300222,China;Department of Psychiatry,Tianjin People's Hospital,Tianjin 300122,China;Biological Psychiatry Department,Tianjin Institute of Mental Health,Tianjin 300222,China)

机构地区：[1]天津市安定医院睡眠科,天津300222 [2]天津市安定医院儿童青少年心理科,天津300222 [3]天津市人民医院精神心理科,天津300122 [4]天津市精神卫生研究所生物精神病学研究室,天津300222

出　　处：《中华行为医学与脑科学杂志》2022年第2期97-103,共7页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金(62027812);天津市临床重点学科(专科)建设项目精神病学基金(ADYK2020003)。

摘　　要：目的探讨青春期睡眠剥夺(sleep deprivation, SD)对成年慢性不可预知性温和应激(chronic unpredictable mild stress, CUMS)模型小鼠抑郁行为及海马突触可塑性的影响。方法将30只清洁级2周龄雄性小鼠按照随机数字表法分为对照组(CON组)、CUMS组和SD+CUMS组, 每组10只。SD+CUMS组小鼠在青春期(3~6周龄)每天进行睡眠剥夺4 h, 并于成年后(9周龄)采用CUMS方法建立抑郁模型;CUMS组小鼠在9周龄时建立CUMS抑郁模型;CON组小鼠不进行睡眠剥夺干预, 不进行CUMS干预。采用体质量、糖水偏爱实验、悬尾实验、强迫游泳实验评价小鼠抑郁行为;采用高尔基染色技术检测小鼠海马CA1脑区基底神经元以及顶端神经元的树突棘密度, 电生理膜片钳技术检测小鼠海马CA1脑区锥体神经元微小兴奋性突触后电流(miniature excitatory postsynaptic current, mEPSC)频率以及幅值的变化。采用Graphpad Prism 7.0软件统计分析和制图, 多组间比较应用单因素方差分析, 进一步两两比较采用Tukey检验。结果 (1)应激造模后, 三组小鼠体质量、糖水偏爱率、强迫游泳不动时间和悬尾时间均差异有统计学意义(F=71.63, 39.82, 44.13, 43.07, 均P<0.01), CUMS组和SD+CUMS组小鼠体质量均低于CON组[(22.92±0.31)g, (20.12±0.27)g, (25.51±0.37)g](均P<0.01), 糖水偏爱率低于CON组[ (63.42±3.33)%, (49.68±3.70)%, (87.40±1.65)%, 均P<0.01], 强迫游泳不动时间长于CON组[ (119.20±12.03) s , (153.80±9.17) s , (34.30±5.32) s;均P<0.01], 悬尾实验不动时间长于CON组[(115.20±8.19 )s, (156.80±4.35) s, (192.00±4.12) s, 均P<0.01]。与CUMS组相比, SD+CUMS组小鼠体质量低(P<0.01), 糖水偏爱率低(P<0.05), 强迫游泳的不动时间和悬尾实验的不动时间均更长(均P<0.01)。(2)在高尔基染色中, 三组小鼠海马CA1区顶端神经元和基底神经元树突棘密度均差异有统计学意义(F=38.41, 41.34, 均P<0.01), 与CON组相比, CUMS组和SD+CUMS组小鼠海马基底�Objective To investigate the effects of early sleep deprivation(SD)on depressive-like behavior and hippocampus synaptic plasticity in adult mice with chronic unpredictable mild stress(CUMS)model.Methods Thirty 2-week-old clean grade male mice were randomly divided into control group(CON group),CUMS group and SD+CUMS group according to the random number table,with 10 mice in each group.The mice in SD+CUMS group were subjected with sleep deprivation for 4 hours once a day during puberty(3~6 weeks old),and then were stimulated by CUMS after adulthood(9 weeks old).The mice in CUMS group were subjected with CUMS at the age of 9 weeks.And the mice in CON group were not given any intervention.The depressive-like behavior was evaluated by body weight,sugar water preference,tail suspension test and forced swimming test.The density of dendritic spines of basal and apical neurons in hippocampal CA1 was measured by Golgi staining,the frequency and amplitude of miniature excitatory postsynaptic current(mEPSC)of pyramidal neurons in the hippocampal CA1 region of mice were measured by electro-physiological patch clamp technique.Graphpad prism 7.0 software was used for statistical analysis and mapping.One-way ANOVA was used for comparison among multiple groups,and Tukey test was used for further pairwise comparison.Results(1)After stress modeling,there were significant differences in body weight,sugar water preference percentage,forced swimming immobility time and tail suspension time among the three groups(F=71.63,39.82,44.13,43.07,all P<0.01).Compared with CON group,the mice in CUMS group and SD+CUMS group had lower body weight((25.51±0.37)g,(22.92±0.31)g,(20.12±0.27)g,both P<0.01),lower sugar water percentage preference((87.40±1.65)%,(63.42±3.33)%,(49.68±3.70)%,both P<0.01),longer immobile time of forced swimming((34.30±5.32)s,(119.20±12.03)s,(153.80±9.17)s,both P<0.01)and longer immobile time of tail suspension test((115.20±8.19)s,(156.80±4.35)s,(192.00±4.12)s,both P<0.01).Compared with CUMS group,SD+CUMS group h

关 键 词：睡眠剥夺 慢性不可预知性温和应激 抑郁 突触可塑性 海马 膜片钳 青春期 小鼠 

分 类 号：R749.4[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]