2013年7月
Calcium-dependent N-cadherin up-regulation mediates reactive astrogliosis and neuroprotection after brain injury
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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- 巻
- 110
- 号
- 28
- 開始ページ
- 11612
- 終了ページ
- 11617
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1073/pnas.1300378110
- 出版者・発行元
- NATL ACAD SCIENCES
Brain injury induces phenotypic changes in astrocytes, known as reactive astrogliosis, which may influence neuronal survival. Here we show that brain injury induces inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ signaling in astrocytes, and that the Ca2+ signaling is required for astrogliosis. We found that type 2 IP3 receptor knockout (IP3R2KO) mice deficient in astrocytic Ca2+ signaling have impaired reactive astrogliosis and increased injury-associated neuronal death. We identified N-cadherin and pumilio 2 (Pum2) as downstream signaling molecules, and found that brain injury induces up-regulation of N-cadherin around the injured site. This effect is mediated by Ca2+-dependent down-regulation of Pum2, which in turn attenuates Pum2-dependent translational repression of N-cadherin. Furthermore, we show that astrocyte-specific knockout of N-cadherin results in impairment of astrogliosis and neuroprotection. Thus, astrocytic Ca2+ signaling and the downstream function of N-cadherin play indispensable roles in the cellular responses to brain injury. These findings define a previously unreported signaling axis required for reactive astrogliosis and neuroprotection following brain injury.
- リンク情報
- ID情報
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- DOI : 10.1073/pnas.1300378110
- ISSN : 0027-8424
- PubMed ID : 23798419
- Web of Science ID : WOS:000321827000087