纹状体注射α-突触核蛋白原纤维加剧 A53T BAC-SNCA 转基因小鼠 REM 睡眠无动症的表型。

Striatal-Inoculation of α-Synuclein Preformed Fibrils Aggravated the Phenotypes of REM Sleep without Atonia in A53T BAC-SNCA Transgenic Mice.

机构信息

Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.

iPSC-Based Drug Discovery and Development Team, RIKEN BioResource Research Center, Kyoto 619-0237, Japan.

出版信息

Int J Mol Sci. 2022 Nov 2;23(21):13390. doi: 10.3390/ijms232113390.

DOI:10.3390/ijms232113390

PMID:36362177

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9656146/

Abstract

Accumulation of α-synuclein (α-syn) is the pathological hallmark of α-synucleinopathy. Rapid eye movement (REM) sleep behavior disorder (RBD) is a pivotal manifestation of α-synucleinopathy including Parkinson's disease (PD). RBD is clinically confirmed by REM sleep without atonia (RWA) in polysomnography. To accurately characterize RWA preceding RBD and their underlying α-syn pathology, we inoculated α-syn preformed fibrils (PFFs) into the striatum of A53T human α-syn BAC transgenic (A53T BAC-SNCA Tg) mice which exhibit RBD-like phenotypes with RWA. RWA phenotypes were aggravated by PFFs-inoculation in A53T BAC-SNCA Tg mice at 1 month after inoculation, in which prominent α-syn pathology in the pedunculopontine nucleus (PPN) was observed. The intensity of RWA phenotype could be dependent on the severity of the underlying α-syn pathology.

摘要

α-突触核蛋白（α-syn）的积累是α-突触核蛋白病的病理标志。快速眼动（REM）睡眠行为障碍（RBD）是包括帕金森病（PD）在内的α-突触核蛋白病的关键表现。通过多导睡眠图中的 REM 睡眠无张力（RWA）来临床确认 RBD。为了准确描述 RBD 之前的 RWA 及其潜在的 α-syn 病理学，我们将 α-syn 预形成纤维（PFF）接种到 A53T 人 α-syn BAC 转基因（A53T BAC-SNCA Tg）小鼠的纹状体中，这些小鼠表现出具有 RWA 的 RBD 样表型。在接种后 1 个月，PFF 接种加重了 A53T BAC-SNCA Tg 小鼠的 RWA 表型，在其中观察到明显的被盖核（PPN）中 α-syn 病理学。RWA 表型的强度可能取决于潜在的 α-syn 病理学的严重程度。