肌肉巨中的上腺信号限制了感染引起的神经元损失
Fanny Matheis1, Paul A Muller1, Christina L Graves1
1Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA.
Cell
|January 11, 2020
概括
感染引起的炎症可以通过损害肠关联神经元 (EANs) 导致长期的肠道问题. 肠道巨细胞通过特定的信号通路保护这些神经元,提供潜在的治疗点.
科学领域:
- 神经胃肠病学
- 免疫学
- 微生物组研究
背景情况:
- 肠关联神经元 (EANs) 与免疫细胞相互作用以维持肠道平衡.
- 功能障碍的神经免疫相互作用与胃肠疾病,如易怒肠综合征和神经退行有关.
- 感染引起的炎症对内在EAN和肌肉巨细胞 (MMs) 的作用的影响尚不完全理解.
研究的目的:
- 研究肠道感染引起的炎症对内在EAN (iEAN) 的长期影响.
- 阐明肠道肌肉巨 (MMs) 在感染期间保护iEANs的作用.
- 确定MMs的神经保护的分子机制.
主要方法:
- 使用了小鼠肠道感染模型.
- 评估了胃肠流动性和IEAN群体.
- 研究了Nlrp6和Casp11炎症酶激活途径.
- 在MM中分析了β2-上腺素受体 (β2-AR) 信号和阿尔金酶1-多胺轴.
主要成果:
- 肠道感染导致了长期的胃肠道症状,包括运动能力下降和刺激性iEANs的丧失.
- 神经元损失是由依赖Nlrp6和Casp11的机制介导的,并且受感染史的影响.
- 微生物群的操纵可以扭转这些影响.
- 肠道MMs通过β2-AR信号调节了一个神经保护程序.
- MMs通过阿尔金酶1-多胺轴保护神经元.
结论:
- 肠道感染可能导致持续的神经元损伤和肠道功能缺陷.
- 在感染后的神经元损伤中,肠道MMs发挥着至关重要的作用.
- 针对MM介导的神经保护通路,如β2-AR和阿尔金酶1-多胺轴,可能为后感染性胃肠道疾病提供治疗策略.
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