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論文
タイトル
タイトル(英)
Severity of Peripheral Infection Differentially Affects Brain Functions in Mice via Microglia-Dependent and -Independent Mechanisms
参照URL
https://researchmap.jp/read0091842/published_papers/44323779
著者
著者(英)
Yen-Phung Le,Kozo Saito,Bijay Parajuli,Kent Sakai,Yuto Kubota,Miho Miyakawa,Youichi Shinozaki,Eiji Shigetomi,Schuichi Koizumi
担当区分
概要
概要(英)
Peripheral infection induces inflammation in peripheral tissues and the brain, impacting brain function. Glial cells are key players in this process. However, the effects of peripheral infection on glial activation and brain function remain unknown. Here, we showed that varying degrees of peripheral infection had different effects on the regulation of brain functions by microglia-dependent and -independent mechanisms. Acute mild infection (one-day LPS challenge: 1LPS) exacerbated middle cerebral artery occlusion (MCAO) injury, and severe infection (four-day LPS challenge: 4LPS) for one week suppressed it. MCAO injury was assessed by triphenyltetrazolium chloride staining. We observed early activation of microglia in the 1LPS and 4LPS groups. Depleting microglia with a colony-stimulating factor-1 receptor (CSF1R) antagonist had no effect on 1LPS-induced brain injury exacerbation but abolished 4LPS-induced protection, indicating microglial independence and dependence, respectively. Microglia-independent exacerbation caused by 1LPS involved peripheral immune cells including macrophages. RNA sequencing analysis of 4LPS-treated microglia revealed increased factors related to anti-inflammatory and neuronal tissue repair, suggesting their association with the protective effect. In conclusion, varying degrees of peripheral inflammation had contradictory effects (exacerbation vs. protection) on MCAO, which may be attributed to microglial dependence. Our findings highlight the significant impact of peripheral infection on brain function, particularly in relation to glial cells.
出版者・発行元
出版者・発行元(英)
MDPI AG
誌名
誌名(英)
International Journal of Molecular Sciences
24
24
開始ページ
17597
終了ページ
17597
出版年月
2023年12月18日
査読の有無
招待の有無
掲載種別
研究論文(学術雑誌)
ISSN
DOI URL
https://doi.org/10.3390/ijms242417597
共同研究・競争的資金等の研究課題
研究者
篠﨑 陽一 (シノザキ ヨウイチ)