自闭症谱系障碍模型小鼠的行为模式及海马神经发生  

Exploring behavioral patterns and hippocampal neurogenesis in autism spectrum disorder mice

作　　者：牛晓洁 刘姣 张欣慰 王泽涛 闫柯企 刘淇源 郝婉云 章培军[1,2] NIU Xiao-jie;LIU Jiao;ZHANG Xin-wei;WANG Ze-tao;YAN Ke-qi;LIU Qi-yuan;HAO Wan-yun;ZHANG Pei-jun(Department of Human Anatomy,Medical College,Shanxi Datong University;Brain Research Institute,Medical College,Shanxi Datong University,Shanxi Datong 037009,China)

机构地区：[1]山西大同大学医学院人体解剖学教研室 [2]山西大同大学医学院脑研究所,山西大同037009

出　　处：《解剖学报》2025年第2期171-179,共9页Acta Anatomica Sinica

基　　金：山西省基础研究计划(自由探索类)基金(20210302123340)。

摘　　要：目的探讨CHD8^(+/-)小鼠的行为模式和海马神经发生的变化情况,为研究改善CHD8^(+/-)小鼠自闭样行为和海马神经发生提供行为学和形态基础。方法野生型(WT)和CHD8^(+/-)小鼠基因鉴定。雄、雌性WT和CHD8^(+/-)小鼠称重,进行3箱社交,自我捋毛,筑巢,Y迷宫自发交替,食物埋藏,旷场和黑白箱行为学实验。2%戊巴比妥钠(2 ml/kg)麻醉,4%多聚甲醛灌注,取脑,摄片,分析脑尺寸的变化;Western blotting及免疫荧光染色检测海马新生神经元的变化。结果Western blotting结果显示,雄、雌性CHD8^(+/-)小鼠的染色体域解旋酶DNA结合蛋白8(CHD8)蛋白水平均较WT小鼠减少。雄、雌性WT和CHD8^(+/-)小鼠体重和脑尺寸差异均无显著性。3箱社交行为实验显示,雄、雌性CHD8^(+/-)小鼠社交障碍(P<0.05);旷场实验结果显示,雄、雌性WT和CHD8^(+/-)小鼠活动总距离差异无显著性,但CHD8^(+/-)小鼠在旷场中心区域的停留时间较WT小鼠显著减少(P<0.01);黑白箱实验显示,雄、雌性CHD8^(+/-)小鼠在白箱内的探索时间较WT小鼠明显减少(P<0.05);而自我捋毛,筑巢,Y迷宫自发交替,食物埋藏实验均无显著变化。此外,Western blotting结果显示,CHD8^(+/-)小鼠海马区双肾上腺皮质激素(DCX)表达减少(P<0.001),免疫荧光染色也显示,CHD8^(+/-)小鼠海马DCX+细胞数量减少(P<0.01)。结论CHD8^(+/-)小鼠表现为社交障碍和焦虑样行为,海马新生神经元数量减少,神经发生障碍。Objective To explore the behavioral patterns and hippocampal neurogenesis of CHD8^(+/-)mice,and to provide behavioral and morphological basis for improving autism like behavior and neurogenesis.Methods Genotype of wild type(WT)and CHD8^(+/-)mice was identified.Weight measurement was conducted on both male and female mice of the WT and CHD8^(+/-)strains.Subsequently,a battery of behavioral tests was administered,which included three⁃chamber test,self⁃grooming test,nesting test,Y⁃maze spontaneous alternation test,food burial test,open⁃field test and light⁃dark transition test.Afterwards,the mice were administered 2%pentobarbital sodium(2 ml/kg)to induce anesthesia.Their brains were frozen with 4%paraformaldehyde,removed for photography and analysis to identify any alterations in brain size.Western blotting and immunofluorescent labeling were used to detect changes in the process of hippocampus neurogenesis.Results Western blotting analysis demonstrated a decrease in the amounts of chromodomain helicase DNA binding protein 8(CHD8)protein in both male and female mice with CHD8^(+/-)genotype,as compared to WT mice.There were no notable disparities in body weight between male and female WT and CHD8^(+/-)mice,as well as in brain size.The three⁃chamber social behavior test revealed that both male and female CHD8^(+/-)mice had social deficiencies(P<0.05).During the open field test,there was no significant difference in the total distance moved by male and female WT and CHD8^(+/-)mice.However,the amount of time spent in the central region was considerably lower in CHD8^(+/-)mice compared to the WT mice(P<0.01).Furthermore,the light⁃dark transition test revealed that both male and female CHD8^(+/-)mice spent considerably less time investigating the white box compared to the WT mice(P<0.05).Nevertheless,there were no notable alterations found in self⁃grooming,nesting,spontaneous alternation of Y⁃maze,and food burial experiments.In addition,Western blotting result demonstrated a significant drop in doublecor

关 键 词：自闭症谱系障碍 染色体域解旋酶DNA结合蛋白8 海马 神经发生 行为学检测 小鼠 

分 类 号：R322[医药卫生—人体解剖和组织胚胎学]