| Autor: |
Ramón, Pérez-Núñez, Alejandro, Chamorro, María Fernanda, González, Pamela, Contreras, Rocío, Artigas, Alejandro H, Corvalán, Brigitte, van Zundert, Christopher, Reyes, Pablo R, Moya, Ana María, Avalos, Pascal, Schneider, Andrew F G, Quest, Lisette, Leyton |
| Rok vydání: |
2021 |
| Zdroj: |
Journal of neuroinflammation. 20(1) |
| ISSN: |
1742-2094 |
| Popis: |
In response to brain injury or inflammation, astrocytes undergo hypertrophy, proliferate, and migrate to the damaged zone. These changes, collectively known as "astrogliosis", initially protect the brain; however, astrogliosis can also cause neuronal dysfunction. Additionally, these astrocytes undergo intracellular changes involving alterations in the expression and localization of many proteins, including αUsing bioinformatics approaches, we analyzed different Gene Expression Omnibus datasets to identify changes occurring in reactive astrocytes as compared to astrocytes from the normal mouse brain. In silico analysis was validated by both qRT-PCR and immunoblotting using reactive astrocyte cultures from the normal rat brain treated with TNF and from the brain of a hSOD1The bioinformatics analysis revealed that genes of the PI3K/AKT signaling pathway were among the most significantly altered in reactive astrocytes. mRNA and protein levels of PI3K, AKT, as well as Cx43, were elevated in reactive astrocytes from normal rats and from hSOD1Here, we identify changes in the PI3K/AKT molecular signaling network and show how they participate in astrogliosis by regulating the HC protein Cx43. Moreover, because HC opening and ATP release are important in astrocyte reactivity, the phosphorylation of Cx43 by AKT and the associated increase in ATP release identify a potential therapeutic window of opportunity to limit the adverse effects of astrogliosis. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink