阴道通路的激活将慢性压力与肠道干细胞功能的下降联系在一起
Guoying Zhang1, Yannan Lian2, Qingguo Li3
1CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China; Jinfeng Laboratory, Chongqing 401329, China.
Cell stem cell
|March 22, 2025
概括
慢性压力通过迷路通路的中央桃体-背部运动核加速肠道干细胞的衰老,独立于其他压力反应. 这种神经通路为与压力相关的肠道问题提供了新的治疗点.
科学领域:
- 神经科学是一个神经科学.
- 胃肠病学 胃肠病学
- 细胞生物学 细胞生物学
背景情况:
- 慢性压力会对肠道健康产生负面影响.
- 连接大脑和肠道的精确神经回路仍然不完全理解.
- 现有的知识通常集中在HPA轴,免疫反应和交感神经系统上.
研究的目的:
- 阐明慢性压力影响肠道干细胞 (ISCs) 的特定神经通路.
- 为了研究迷路 (CeA-DMV) 中枢桃体-背部运动核 (CeA-DMV) 途径在压力诱导的肠道功能障碍中的作用.
- 确定压力诱导的ISC衰老背后的分子机制.
主要方法:
- 利用慢性压力的动物模型.
- 研究了CeA-DMV神经路径.
- 检查了ISC功能,茎度和衰老标志物.
- 分析了分子信号通路,包括胆固醇信号和MAPK.
- 评估了微生物群,HPA轴,免疫系统和SNS的作用.
主要成果:
- 慢性压力激活了CeA-DMV通路,导致ISCs的过早衰老和干部受损.
- 这种效应独立于微生物群,HPA轴,免疫反应和SNS.
- DMV激活触发了肠道神经元的乙胆释放,通过CHRM3.3对ISCs起作用.
- 这种信号级联激活了p38 MAPK通路,导致ISC的生长停止和线粒体分裂.
结论:
- 一个新的神经通路 (CeA-DMV) 将慢性压力与肠道干细胞衰老联系起来.
- 通过CHRM3和p38 MAPK进行胆固醇信号传递是压力诱导的ISC功能障碍的一个关键机制.
- 针对DMV相关的阴道通路,为与压力相关的肠道疾病提供了潜在的治疗策略.
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