MeCP2自闭小鼠发育过程中的听觉脑干反应  

Auditory brainstem responses during development of MeCP2 autistic mice

作　　者：闫素梅[1] 钱绍文 胡先丽 庞瑞旗 石峙岳 周艺[1] YAN Sumei;QIAN Shaowen;HU Xianli;PANG Ruiqi;SHI Zhiyue;ZHOU Yi(Department of Neurobiology,College of Basic Medical Sciences,Army Medical University(Third Military Medical University),Chongqing,400038;Advanced Institute for Brain and Intelligence,Guangxi University,Nanning,Guangxi Zhuang Autonomous Region,530004;Department of Surgery,No.953 Hospital of PLA,Shigatse,Tibet Autonomous Region,857000,China)

机构地区：[1]陆军军医大学(第三军医大学)基础医学院神经生物学教研室,重庆400038 [2]广西大学脑与智能研究中心,南宁530004 [3]陆军第953医院外科,西藏日喀则857000

出　　处：《陆军军医大学学报》2022年第2期103-109,共7页Journal of Army Medical University

基　　金：国家自然科学基金面上项目(31970932,31771152)。

摘　　要：目的探索甲基-CpG结合蛋白2(methyl CpG binding protein 2,MeCP2)过表达小鼠(MeCP2-Tg1,自闭模型小鼠)发育过程中的听力变化。方法在8周和14周对MeCP2-Tg1小鼠(Tg1组)和WT小鼠(WT组)进行三箱社交行为测试,检测MeCP2-Tg1小鼠的社交功能。在社交行为异常发生前后的5个发育节点(4、8、12、16、20周)记录click及纯音刺激诱发的听觉脑干电位,评估不同发育阶段Tg1小鼠的听力敏感性(阈值)、神经传导速度(潜伏期)和反应强度(波幅)。结果①与WT组相比,Tg1组小鼠在4周和12周对24 kHz纯音刺激表现出更高的敏感性(P<0.05),20周时对8 kHz纯音刺激表现出更低的阈值(P<0.05),但阈值降低现象在发育进程中并不持续。②Tg1组小鼠在整个发育过程中的神经传导速度正常。③与WT组相比,Tg1组小鼠表征上橄榄核的Ⅲ波幅值在8周(含)之前正常,但12周(含)之后表现出显著的持续性升高(P<0.05);表征听觉下丘的Ⅴ波幅值在8周(含)之前显著偏低(P<0.05),但12周及之后则恢复正常。结论MeCP2-Tg1小鼠听觉脑干反应在发育过程中出现异常,主要表现为在不同发育时期对声刺激反应幅度的增高/降低,且听力异常的发生早于社交行为异常发生。Objective To explore the hearing changes in an autism model mice[MeCP2-Tg1 mice,with overexpression of methyl-CpG binding protein 2(MeCP2)]during development.Methods Three-chamber social test was used to assess the social ability of MeCP2-Tg1 mice and wild-type mice at 8 and 14 weeks after born.Auditory brainstem responses evoked by click and pure tone stimulus were recorded at 5 development nodes(4,8,12,16 and 20 weeks)before and after the onset of abnormal social behaviors to assess hearing sensitivity(threshold),neural conduction velocity(latency)and response level(amplitude)in MeCP2-Tg1 mice at different developmental stages.Results①Tg1 mice showed higher sensitivity to 24 kHz stimulus at 4 and 12 weeks(P<0.05),and lower hearing threshold to 8 kHz stimulus at 20 weeks as compared with wild-type mice(P<0.05),but the threshold reduction did not persist over the course of development.②Tg1 mice had normal neural conduction velocity throughout development.③Compared with the wild-type mice,the amplitude of waveⅢ,which characterizes the superior olivary complex,was normal up to 8 weeks(inclusive)but showed a significant and persistent increase after 12 weeks(inclusive)(P<0.05);the amplitude of wave V,which characterizes the auditory inferior colliculus,was significantly lower up to 8 weeks(inclusive)(P<0.05)but showed normal after 12 weeks(inclusive).Conclusion The auditory brainstem responses of MeCP2-Tg1 mice are abnormal during development,mainly in the form of increased/decreased amplitude of responses to acoustic stimuli at different developmental periods,and the onset of hearing abnormalities precedes the onset of social behavior abnormalities.

关 键 词：自闭症谱系障碍 听力异常 听觉脑干诱发电位 甲基-CpG结合蛋白2 

分 类 号：R338.8[医药卫生—人体生理学] R339.16[医药卫生—基础医学]