NMDA受体3A亚基基因敲除对小鼠焦虑和抑郁样行为的影响  

GRIN3A knockout affecting anxiety and depression like behaviors in mice

作　　者：刘文嵚 陈静 张萌萌 孔祥如[2] 蒋林[3] 刘灿 修芸[1] Liu Wenqin;Chen Jing;Zhang Mengmeng;Kong Xiangru;Jiang Lin;Liu Can;Xiu Yun(Institue of Life Science,Chongqing Medical University,Chongqing 400016,China;Department of Pediatric Surgical Oncology,Children's Hospital,Chongqing Medical University,Chongqing 400016,China;Lab Teaching&Management Center,Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆医科大学生命科学研究院,重庆400016 [2]重庆医科大学附属儿童医院小儿肿瘤外科,重庆400016 [3]重庆医科大学实验室教学管理中心,重庆400016

出　　处：《神经解剖学杂志》2022年第4期403-410,共8页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(81301149)。

摘　　要：目的:观察N-甲基-D-天冬氨酸受体3A亚基(NR3A)编码基因GRIN3A敲除对小鼠焦虑和抑郁样行为的影响,以探讨NR3A亚基在抑郁症中的作用。方法:通过CRISPR/Cas9技术敲除C57BL/6N小鼠GRIN3A基因第2个外显子,繁殖获得足够数量的各组小鼠。使用糖水偏好实验,悬尾实验和强迫游泳实验检测小鼠抑郁样行为;使用高架O迷宫实验和旷场实验检测小鼠焦虑样行为。结果:雄性小鼠行为学显示:悬尾实验中GRIN3A^(-/-)小鼠不动时间比野生型小鼠长(P<0.01);糖水偏好实验GRIN3A^(-/-)小鼠糖水偏好(P<0.05)、总饮水量(P<0.01)和糖水饮用量(P<0.01)低于野生型小鼠,GRIN3A^(+/-)小鼠糖水偏好低于野生型小鼠(P<0.01),纯水饮用量高于野生型小鼠(P<0.01);高架O迷宫实验GRIN3A^(-/-)小鼠在封闭象限停留时间比野生型小鼠长;旷场实验GRIN3A^(-/-)小鼠粪便数多于野生型小鼠。雌性小鼠行为学显示:强迫游泳实验中GRIN3A^(-/-)小鼠不动时间比野生型小鼠长(P<0.01);糖水偏好实验GRIN3A^(-/-)小鼠糖水饮用量(P<0.01)和总饮水量(P<0.01)低于野生型小鼠。结论:雄性GRIN3A^(-/-)小鼠表现出明显的抑郁样和焦虑样行为,雄性GRIN3A^(+/-)小鼠和雌性GRIN3A^(-/-)小鼠表现出抑郁样行为。Objective:To observe the effect of GRIN3 A like deletion of N-methyl-D-aspartate receptor(NMDAR)3 A subunit(NR3 A)on depression and anxiety behavior in mice,so as to explore the role of NR3 A subunit in depression.Methods:The second exon of GRIN3 A gene in C57 BL/6 N mice was knocked out by CRISPR/Cas9 technique.The depressive-related behaviors of mice were evaluated by sucrose preference test(SPT),tail suspension test(TST)and force swimming test(FST);The anxiety-related behaviors of mice were evaluated by elevated O maze test(EOM)and open field test(OFT).Results:The behavior of male mice showed that the immobility time of GRIN3 A^(-/-)mice was longer than that of wild-type(WT)mice in tail suspension test(P<0.01);In SPT,the sucrose water preference percentage(P<0.05),liquid consumption(P<0.01)and sucrose water consumption(P<0.01)of GRIN3 A^(-/-)mice were lower than those of WT mice,GRIN3 A^(+/-)mice had lower sucrose water preference percentage(P<0.01)and higher pure water consumption(P<0.01)than wild-type mice.The residence time of GRIN3 A^(-/-)mice in the closed arm was longer than that of WT mice in EOM.In OFT,the number of feces of GRIN3 A^(-/-)mice was more than that of WT mice.The behavior of female mice showed that the immobility time of GRIN3 A^(-/-)mice was longer than that of WT mice in FST(P<0.01);sucrose water consumption(P<0.01)and liquid consumption(P<0.01)of GRIN3 A^(-/-)mice were lower than those of WT mice.Conclusion:Male GRIN3 A^(-/-)mice showed depression-related behaviors and anxiety-related behaviors,while male GRIN3 A^(+/-)mice and female GRIN3 A^(-/-)mice only showed depression-related behaviors,but without anxiety-related behaviors.

关 键 词：N-甲基-D-天冬氨酸受体3A亚基 GRIN3A基因 焦虑 抑郁 小鼠 

分 类 号：R749.4[医药卫生—神经病学与精神病学]