p150Glued缺失导致小鼠纹状体多巴胺能轴突变性  

p150Glued deficiency leads to striatal dopaminergic axonal degeneration of mice

作　　者：郑佳音 王昕宇 于佳[1] Zheng Jiayin;Wang Xinyu;Yu Jia(Institute of Geriatrics and Rehabilitation,Beijing Geriatric Hospital,Beijing 100095,China)

机构地区：[1]北京老年医院老年医学基础研究中心,北京100095

出　　处：《脑与神经疾病杂志》2025年第2期93-98,共6页Journal of Brain and Nervous Diseases

基　　金：北京市自然科学基金资助项目(7242081);国家自然科学基金资助项目(82071438);北京老年医院老年医学科研专项(2022bjlnyy-qh-1)。

摘　　要：目的探讨佩里综合征相关蛋白p150Glued在小鼠中脑多巴胺能神经元及纹状体多巴胺能神经元轴突中的作用。方法通过免疫荧光染色技术观察中脑多巴胺能神经元中特异性敲除p150Glued的cKO小鼠和对照组(Ctrl)小鼠中脑多巴胺能神经元的数目变化及纹状体中多巴胺能神经元轴突的结构。结果cKO小鼠中脑中ALDH1A1阳性和ALDH1A1阴性多巴胺能神经元均显著丢失,纹状体中ALDH1A1阳性和ALDH1A1阴性多巴胺能神经元轴突也显著丢失。cKO小鼠纹状体中多巴胺能神经元轴突明显肿胀,且肿胀的轴突中存在异常积累的VAMT2阳性囊泡和Cathepsin D阳性结构。结论p150Glued为多巴胺能神经元的存活及多巴胺能神经元轴突结构的完整性所必需,p150Glued缺失可导致多巴胺能神经元轴突运输功能障碍。Objective To explore the role of the Perry syndrome-associated protein p150Glued in midbrain dopaminergic neurons and striatal dopaminergic axons of mouse.Methods The number of midbrain dopaminergic neurons and the structure of striatal dopaminergic axons in cKO and Ctrl mice were observed by immunofluorescence staining.Results Compared to Ctrl mice,the numbers of ALDHIA1-positive and ALDH1A1-negative dopaminergic neurons were significant decreased in the midbrain of cKO mice.The ALDH1A1-positive and ALDH1A1-negative dopaminergic axons were also significantly lost in the striatum of cKO mice.We also observed that the striatal dopaminergic axons of cKO mice were markedly swollen,and there was abnormal accumulation of VAMT2-positive vesicles and Cathepsin D-positive structures in the swollen dopaminergic axons.Conclusion p150Glued is necessary for the survival of dopaminergic neurons and the integrity of dopaminergic axons structure in mice.Moreover,p150Glued deficiency can lead to transport dysfunction in the dopaminergic axons.

关 键 词：p150Glued 佩里综合征 多巴胺能神经元 纹状体 多巴胺能轴突 

分 类 号：R743.3[医药卫生—神经病学与精神病学]