佩里综合征动物模型多巴胺转运体缺陷的超高分辨率显微成像研究  

Study of dopamine transporter defects in Perry syndrome animal model by Airyscan microscopy imaging

作　　者：杨璇 贾炳泉 郑佳音 王昕宇 Yang Xuan;Jia Bingquan;Zheng Jiayin;Wang Xinyu(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》2024年第4期246-250,共5页Journal of Brain and Nervous Diseases

基　　金：国家自然科学基金资助项目(82071438);北京市百千万人才工程资助项目(2007002);北京老年医院老年医学科研专项(202ZbjlnYY-9h-1,2020bjnyy-自-3)。

摘　　要：目的探讨佩里综合征模型小鼠中脑多巴胺能神经元纹状体多巴胺转运体(DAT)缺陷的亚细胞机制。方法利用免疫荧光染色法,采用Airyscan超高分辨率显微成像和三维成像技术,检测佩里综合征模型小鼠中脑多巴胺能神经元中DAT表达分布情况。结果佩里综合征模型小鼠中脑多巴胺能神经元部分树突发生病理性肿胀,而在这些肿胀中有荧光强度显著增加的异常内质网结构,以及异常增多的溶酶体。大量的DAT呈点状定位于树突异常肿胀内,且有相当数量的DAT与异常内质网结构,或异常增多的溶酶体共定位。结论佩里综合征模型小鼠中脑多巴胺能神经元中DAT潴留于树突肿胀内质网中,不能有效的输出和运送至纹状体发挥功能;同时树突肿胀中DAT降解增多,进一步加剧了纹状体DAT缺陷。Objective To explore the subcellular mechanism of DAT defects in midbrain dopaminergic neurons of Perry syndrome mice.Methods Immunofluorescence staining,airyscan microscopy and three-dimensional imaging techniques were used to detect the distribution of DAT in midbrain dopaminergic neurons of Perry syndrome mice.Results Pathological dendritic swellings were observed in midbrain dopaminergic neurons of Perry syndrome mice.Abnormal endoplasmic reticulum structures with high fluorescence intensity and a large number of lysosomes were observed in these swellings.Massive DAT vesicles localized in the pathological dendritic swellings,with part of them colocalized with abnormal endoplasmic reticulum or lysosomes.Conclusion DAT retained in abnormal endoplasmic reticulum within pathological dendritic swellings in midbrain dopaminergic neurons of Perry syndrome mice.As a result,DAT cannot be effectively exported and transported to the striatum.Moreover,the degradation of DAT increased in dendritic swelling,which further exacerbated the DAT defects.

关 键 词：帕金森综合征 佩里综合征 多巴胺转运体 中脑多巴胺能神经元 

分 类 号：R742.5[医药卫生—神经病学与精神病学]