摘要
目的 探究线粒体相关分子mRNA在小脑浦肯野细胞中的分布.方法 利用转基因技术制备Pcp2-tdTomato小鼠标记浦肯野细胞,采用RNAscope技术原位检测线粒体相关分子Mfn2、Mfn1、Ucp4、Drp1、Ucp2、Mcu和Nclx的mRNA.结果 本研究结果显示,Mfn2、Mfn1、Ucp4和Drp1在浦肯野细胞体中高表达(Bin3>10%),而 Ucp2、Mcu和 Nclx 表达较少.Mfn2、Mfn1、Ucp4、Drp1、Ucp2、Mcu 和 Nclx 在树突中的表达量较少.结论 目前的研究重点是开发新的和更特异性的分子来调节浦肯野细胞的活性,并为浦肯野细胞相关疾病打开治疗窗口.潜在药物靶点的分子鉴定、作用机制及其活性的结构基础对促进临床前开发至关重要.
Abstract
Objective To investigate the distribution of mitochondria-associated molecule mRNA in cerebellar Purkinje cells.Methods Transgenic technology was used to prepare Pcp2-tdTomato mouse labeled Purkinje cells.The mRNAs of mitochondria-associated molecules Mfn2,Mfn1,Ucp4,Drp1,Ucp2,Mcu and Nclx were detected in situ by RNAscope technique.Results The results of this study showed that Mfn2,Mfn1,Ucp4 and Drp1 were highly expressed in Purkinje cell body(Bin 3>10%).However,Ucp2,Mcu and Nclx were less expressed.In addition,Mfn2,Mfn1,Ucp4,Drp1,Ucp2,Mcu and Nclx were less expressed in dendrites.Conclusion Current research focuses on developing new and more specific molecules to regulate the activity of Purkinje cells and opening therapeutic windows for Purkinje cells related diseases.The molecule identification of potential drug targets,mechanisms of action,and structural basis of their activity will crucially promote preclinical development.