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Pharmacological and genetic inhibition of translocator protein 18 kDa ameliorated neuroinflammation in murine endotoxemia model
https://repo.qst.go.jp/records/81463
https://repo.qst.go.jp/records/81463e15c8c5d-7057-4031-988e-f5d4a65bdcc1
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2020-11-24 | |||||
| タイトル | ||||||
| タイトル | Pharmacological and genetic inhibition of translocator protein 18 kDa ameliorated neuroinflammation in murine endotoxemia model | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Giga, Hiroshi
× Giga, Hiroshi× Ji, Bin× Kikutani, Kazuya× Fukuda, Shuji× Kitajima, Takashi× Katsumata, Seishi× Matsumata, Miho× Suhara, Tetsuya× Yamawaki, Shigeto× Shime, Nobuaki× Hosokawa, Koji× Aizawa, Hidenori× Ji, Bin× Tetsuya, Suhara |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction associated with sepsis. The development of an effective strategy for early diagnosis and therapeutic intervention is essential for the prevention of poor prognosis of SAE. Translocator protein 18 kDa (TSPO) is a mitochondrial protein implicated in steroidogenesis and inflammatory responses. Despite accumulating evidence that implicates TSPO in the neuroinflammatory response of the central nervous system, the possible role of TSPO in SAE remains unclear. Aim of this study is to address a role of TSPO in neuroinflammation using mice 24 h after systemic injection of lipopolysaccharide (LPS), which consistently demonstrated microglial activation and behavioral inhibition. Quantitative polymerase chain reaction analysis revealed that hippocampal TSPO expression was induced following the systemic LPS injection, associated with an increase in pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-1β. Interestingly, pretreatment with the TSPO antagonist, ONO-2952, or germ-line deletion of the TSPO gene exhibited an anti-inflammatory effect with significant suppression of LPS-induced production of those cytokines. These effects demonstrated by the ONO-2952 or TSPO knockout were associated with significant recovery from behavioral inhibition, as shown by improved locomotor activity in the open field analysis. Histological analysis revealed that ONO-2952 pretreatment suppressed the LPS-induced activation of TSPO-expressing microglia in the hippocampus of mice. Collectively, these results suggest that TSPO plays a critical role in the SAE mouse model. Based on this finding, monitoring TSPO activity, as well as the progress of endotoxemia and its sequelae in the animal model, would deepen our understanding of the underlying molecular mechanism of SAE. | |||||
| 書誌情報 |
SHOCK 巻 56, 号 1, p. 142-149, 発行日 2020-12 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1073-2322 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 33351449 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1097/SHK.0000000000001703 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://journals.lww.com/shockjournal/Abstract/2021/07000/Pharmacological_and_Genetic_Inhibition_of.17.aspx | |||||
