灵长类帕金森病模型中基底神经节D1中型多棘神经元化学遗传激活及行为评估方案

Protocol for chemogenetic activation of basal ganglia D1-MSNs and behavioral assessments in a primate Parkinson's disease model.

作者信息

Chen Yefei, Hong Zexuan, Yan Ting, Zhu Yuyuan, Lin Jianbang, Liu Taian, Guo Ming, Li Mengqi, Feng Shijing, Li Ronghui, Zhang Jianqing, Chen Siyang, Yang Yi, Li Yuantao, Lu Zhonghua

机构信息

Department of Anesthesiology, Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen 518027, China; Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen Technological Research Center for Primate Translational Medicine, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.

Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen Technological Research Center for Primate Translational Medicine, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Research Center for Primate Neuromodulation and Neuroimaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.

出版信息

STAR Protoc. 2024 Dec 20;5(4):103470. doi: 10.1016/j.xpro.2024.103470. Epub 2024 Dec 6.

DOI:10.1016/j.xpro.2024.103470

PMID:39644495

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11656076/

Abstract

A circuit-based gene therapy strategy for Parkinson's disease (PD) has been shown to significantly reverse core symptoms in both murine and primate PD models. Here, we present a comprehensive workflow to specifically manipulate dopamine receptor D-expressing medium spiny neurons by retrograde adeno-associated virus (AAV) transduction and chemogenetic activation using a designer toolkit. We describe steps for AAV injections and PD primate model induction. We then detail behavioral measurements to assess the therapeutic efficacy of the therapy for motor symptoms.

摘要

一种基于回路的帕金森病（PD）基因治疗策略已被证明能在小鼠和灵长类PD模型中显著逆转核心症状。在此，我们展示了一个全面的工作流程，通过逆行腺相关病毒（AAV）转导和使用设计工具包进行化学遗传激活，特异性地操纵表达多巴胺受体D的中等棘状神经元。我们描述了AAV注射和PD灵长类模型诱导的步骤。然后，我们详细介绍行为测量方法，以评估该疗法对运动症状的治疗效果。