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論文
- タイトル
- タイトル（英）
- Disease-relevant upregulation of P2Y1 receptor in astrocytes enhances neuronal excitability via IGFBP2
- 参照URL
- https://researchmap.jp/read0091842/published_papers/47604725
- 著者
- 著者（英）
- Eiji Shigetomi,Hideaki Suzuki,Yukiho J. Hirayama,Fumikazu Sano,Yuki Nagai,Kohei Yoshihara,Keisuke Koga,Toru Tateoka,Hideyuki Yoshioka,Youichi Shinozaki,Hiroyuki Kinouchi,Kenji F. Tanaka,Haruhiko Bito,Makoto Tsuda,Schuichi Koizumi
- 担当区分
- 概要
- 概要（英）
- Abstract Reactive astrocytes play a pivotal role in the pathogenesis of neurological diseases; however, their functional phenotype and the downstream molecules by which they modify disease pathogenesis remain unclear. Here, we genetically increase P2Y<sub>1</sub> receptor (P2Y1R) expression, which is upregulated in reactive astrocytes in several neurological diseases, in astrocytes of male mice to explore its function and the downstream molecule. This astrocyte-specific P2Y1R overexpression causes neuronal hyperexcitability by increasing both astrocytic and neuronal Ca<sup>2+</sup> signals. We identify insulin-like growth factor-binding protein 2 (IGFBP2) as a downstream molecule of P2Y1R in astrocytes; IGFBP2 acts as an excitatory signal to cause neuronal excitation. In neurological disease models of epilepsy and stroke, reactive astrocytes upregulate P2Y1R and increase IGFBP2. The present findings identify a mechanism underlying astrocyte-driven neuronal hyperexcitability, which is likely to be shared by several neurological disorders, providing insights that might be relevant for intervention in diverse neurological disorders.
- 出版者・発行元
- 出版者・発行元（英）
- Springer Science and Business Media LLC
- 誌名
- 誌名（英）
- Nature Communications
- 巻
- 15
- 号
- 1
- 開始ページ
- 終了ページ
- 出版年月
- 2024年8月8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/10.1038/s41467-024-50190-7
- 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)