实验性结肠炎的特异性免疫调节驱动肠道α-synuclein积累,并触发与年龄相关的帕金森症类似的大脑病理
Stefan Grathwohl1, Emmanuel Quansah2, Nazia Maroof1
1Roche Pharma Research and Early Development, Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Basel, Switzerland Switzerland.
Free neuropathology
|June 7, 2023
概括
肠道炎症,特别是硫酸 (DSS) 大肠炎,可以触发肠道和大脑中的α-synuclein (αSyn) 积累,可能引发帕金森病 (PD) 病理. 巨细胞信号影响这个过程,影响神经元损失.
科学领域:
- 神经科学是一个神经科学.
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
背景情况:
- 肠道神经系统 (ENS) 中的α-synuclein (αSyn) 聚合可能在帕金森病 (PD) 大脑病理之前几十年.
- 肠道炎症在启动ENS和大脑αSyn病理中的作用尚不清楚.
研究的目的:
- 研究不同类型和严重程度的肠道炎症如何影响ENS中的αSyn积累.
- 确定实验性结肠炎对αSyn脑病理和神经元损失的发展的影响.
主要方法:
- 在αSyn转基因和野生型小鼠中使用硫酸 (DSS) 诱导实验性结肠炎.
- 免疫和基因表达分析评估了在肠道和大脑中的αSyn积累.
- 巨细胞相关途径在遗传和药理上受到调节.
主要成果:
- 一次强烈或持续的轻度DSS大肠炎,但不是短期轻度大肠炎或LPS诱导的炎症,触发了ENS中的αSyn积累.
- 巨细胞通路的调节影响了肠道αSyn.的严重程度.
- 在年轻小鼠中的实验性结肠炎加剧了中脑αSyn积累和老年小鼠中的尼格拉尔神经元损失.
结论:
- 特定的肠道炎症类型和严重程度,通过单细胞/巨细胞信号传导,涉及到PD的开始和进展.
- 肠道αSyn积累和随后的脑病理可能与肠道炎症有关.
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