| First Author | Kanemaru K | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 28 | Pages | 11612-7 |
| PubMed ID | 23798419 | Mgi Jnum | J:198696 |
| Mgi Id | MGI:5499019 | Doi | 10.1073/pnas.1300378110 |
| Citation | Kanemaru K, et al. (2013) Calcium-dependent N-cadherin up-regulation mediates reactive astrogliosis and neuroprotection after brain injury. Proc Natl Acad Sci U S A 110(28):11612-7 |
| abstractText | 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 Ca(2+) signaling in astrocytes, and that the Ca(2+) signaling is required for astrogliosis. We found that type 2 IP3 receptor knockout (IP3R2KO) mice deficient in astrocytic Ca(2+) 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 Ca(2+)-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 Ca(2+) 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. |
