转录因子TWIST1干扰神经发生对睡眠剥夺小鼠抑郁样行为的影响  

Depression-like behavior in sleep-deprived mice caused by interference of transcription factor TWIST1 on neurogenesis

作　　者：白布加甫·高娃 热依汗古丽·阿不来提 林凯[1] Baibujiafu Gaowa;Reyihanguli Abulaiti;LIN Kai(Third Department of Clinical Psychology,the Fourth People’s Hospital of Urumqi City,Xinjiang,Urumqi 830002,China;不详)

机构地区：[1]新疆维吾尔自治区乌鲁木齐市第四人民医院临床心理三科,830002 [2]新疆维吾尔自治区乌鲁木齐市第四人民医院精神三科,830002

出　　处：《河北医药》2023年第9期1285-1290,共6页Hebei Medical Journal

基　　金：新疆维吾尔自治区自然科学基金项目(编号:2021D01C107)。

摘　　要：目的探究转录因子TWIST1对睡眠剥夺诱发抑郁样行为小鼠神经发生的影响。方法将小鼠随机分为对照(Con)组,对照+LV-sh TWIST1(Con+LV-sh TWIST1)组,睡眠剥夺(SD)组,睡眠剥夺+LV-sh TWIST1(SD+LV-sh TWIST1)组。通过LV-shTWIST1降低小鼠脑组织中TWIST1表达,采用睡眠剥夺构建小鼠抑郁症模型,连续7 d,期间每天腹腔注射50 mg/kg BrdU溶液。通过糖水偏好测试、悬尾测试、强迫游泳测试与旷场测试检测小鼠抑郁样症状,Morris水迷宫检测小鼠学习、记忆能力,Western blot检测神经发生相关蛋白表达,电生理测试检测突触可塑性,免疫荧光检测神经发生情况。结果与Con组比较,SD组小鼠糖水偏好率与旷场测试评分明显减少(P<0.05),悬尾与游泳不动时间明显增加(P<0.05),Morris水迷宫中首次到达平台时间明显增加(P<0.05)。然而,与SD组比较,SD+LV-shTWIST1组糖水偏好率与旷场测试评分明显增加(P<0.05),悬尾与游泳不动时间明显减少(P<0.05),Morris水迷宫中首次到达平台时间明显减少(P<0.05)。此外,Western blot检测TWIST1表达明显降低的同时Wnt3a与β-catenin蛋白表达明显增加,与此同时,fEPSP斜率明显升高且BrdU阳性细胞数明显增加。结论睡眠剥夺造成的小鼠抑郁样行为与脑组织中TWIST1表达升高相关,通过降低TWIST1表达能够激活Wnt3a/β-catenin信号通路,促进神经发生,达到改善小鼠抑郁样行为的作用。Objective To explore the effects of transcription factor TWIST1 on neurogenesis in mice with depression-like behavior induced by sleep deprivation.Methods Mice were randomly divided into the group control(Con)group,control+LV sh TWIST1(Con+LV sh TWIST1)group,sleep deprivation(SD)group,and sleep deprivation+LV sh TWIST1(SD+LV sh TWIST1)group.The expression of TWIST in brain tissues of mice was reduced through LV shTWIST1,the mouse depression model was set up by sleep deprivation for 7 days,and 50mg/kg of BrdU solution was intraperitoneally injected on a daily basis.Depression-like symptoms in mice were detected by the sucrose preference test,tail suspension test,forced swimming test and open field test.The learning and memory abilities of mice were detected by Morris water maze.The expression of neurogenesis-related proteins was detected by Western blot,synaptic plasticity was detected by electrophysiological tests,and the neurogenesis was detected by immunofluorescence.Results Compared with the Con group,the sucrose preference rate and open-field test score in the SD group were significantly decreased(P<0.05),the immobility time of tail suspension and forced swimming was significantly increased(P<0.05),and the duration of access to the platform for the first time in the Morris water maze was significantly increased(P<0.05).Compared with the SD group,the sucrose preference rate and open-field test score in SD+LV shTWIST1 group were significantly increased(P<0.05),the immobility time of tail suspension and forced swimming was significantly decreased(P<0.05),and the duration of access to the platform for the first time in the Morris water maze was significantly reduced(P<0.05).Moreover,the results of Western blot showed that the expression of Wnt3a andβ-catenin proteins were significantly increased,while the expression of TWIST1 was significantly decreased,the slope of fEPSP was significantly increased,and the number of BrdU positive cells was significantly increased.Conclusion The depressive-like behavior of mice

关 键 词：TWIST1 睡眠剥夺 抑郁样行为 学习、记忆能力 神经发生 

分 类 号：R749.42[医药卫生—神经病学与精神病学]