实验性自身免疫性脑脊髓炎
星形胶质细胞
水通道蛋白4
免疫学
多发性硬化
脑脊髓炎
化学
肠道菌群
生物
中枢神经系统
生物化学
内分泌学
作者
Xiuli Lin,YuFeng Peng,NULL AUTHOR_ID,Wuhui He,Wenyuan Guo,Junmin Feng,NULL AUTHOR_ID,NULL AUTHOR_ID,Pingyi Xu
标识
DOI:10.1007/s00018-024-05332-x
摘要
Abstract The function of astrocytes in response to gut microbiota-derived signals has an important role in the pathophysiological processes of central nervous system (CNS) diseases. However, the specific effects of microbiota-derived metabolites on astrocyte activation have not been elucidated yet. Experimental autoimmune encephalomyelitis (EAE) was induced in female C57BL/6 mice as a classical MS model. The alterations of gut microbiota and the levels of short-chain fatty acids (SCFAs) were assessed after EAE induction. We observed that EAE mice exhibit low levels of Allobaculum , Clostridium_IV , Clostridium_XlVb , Lactobacillus genera, and microbial-derived SCFAs metabolites. SCFAs supplementation suppressed astrocyte activation by increasing the level of tryptophan (Trp)-derived AhR ligands that activating the AhR. The beneficial effects of SCFAs supplementation on the clinical scores, histopathological alterations, and the blood brain barrier (BBB)-glymphatic function were abolished by intracisterna magna injection of AAV-GFAP-shAhR. Moreover, SCFAs supplementation suppressed the loss of AQP4 polarity within astrocytes in an AhR-dependent manner. Together, SCFAs potentially suppresses astrocyte activation by amplifying Trp-AhR-AQP4 signaling in EAE mice. Our study demonstrates that SCFAs supplementation may serve as a viable therapy for inflammatory disorders of the CNS.
科研通智能强力驱动
Strongly Powered by AbleSci AI