外围HMGB1与与疾病相关的星球细胞和粉样蛋白相关的O3病理有关
Chandrama Ahmed1, Hendrik J Greve1, Carla Garza-Lombo1
1Department of Pharmacology and Toxicology, Indiana University School of Medicine, The Stark Neurosciences Research Institute, Indianapolis, Indiana, USA.
概括
臭氧暴露会通过改变星体细胞和它们与微质细胞的相互作用,使阿尔茨海默氏病的病理状况恶化. 周围髓状细胞HMGB1对于调节这些臭氧诱导的变化至关重要,提供了潜在的治疗点.
科学领域:
- 神经科学是一个神经科学.
- 环境健康 环境健康
- 免疫学 免疫学 免疫学
背景情况:
- 臭氧 (O3) 是一种空气污染物,与阿尔茨海默病 (AD) 风险增加有关.
- 肺-大脑轴在O3相关的质和粉样蛋白病理中发挥作用.
- 疾病相关天体细胞 (DAA) 在O3诱导的AD病原发生中的特定作用尚不清楚.
研究的目的:
- 调查O3暴露对AD小鼠模型中天体细胞表型和功能的影响.
- 探索外围髓质细胞高流动性组盒1 (HMGB1) 在O3诱导的星球细胞变化中的作用.
- 阐明空气污染对阿尔茨海默症病理生物学贡献的基础机制.
主要方法:
- 空间转录组学和蛋白质组学被用于5xFAD小鼠中O3诱导的天体细胞表型的特征.
- Hmgb1的LysM-Cre的小鼠被用来评估HMGB1在外围髓状细胞中的功能.
- 分析包括天体细胞和斑块计数,蛋白质组和转录组分析,以及天体细胞-微细胞相互作用的评估.
主要成果:
- 在5xFAD小鼠中,O3暴露增加了星细胞和粉样质斑块的数量.
- 暴露于O3阻碍了天体细胞蛋白质反应,增强了DAA转录特征,并增加了天体细胞-微细胞接触.
- 在暴露于O3的小鼠中观察到支气管膜洗免疫细胞HMGB1表达的减少和DAA mRNA标记的失调,特别是那些在髓质细胞中缺乏HMGB1的小鼠.
结论:
- 星球细胞和外围髓状细胞是肺-大脑轴的关键组成部分,在介导O3对AD病理学的影响中发挥作用.
- 周围髓状细胞中的HMGB1是O3诱导的DAA表型的关键调节者.
- 这些发现确定了将空气污染与AD联系起来的新机制,并建议HMGB1作为潜在的治疗点.
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