![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
|
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
9MB | |
|
PDF (Supporting Information)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
6MB |
| Item Type: | Article |
|---|---|
| Title: | HIF prolyl hydroxylase 2/3 deletion disrupts astrocytic integrity and exacerbates neuroinflammation |
| Creators Name: | Rosiewicz, K.S. and Muinjonov, B. and Kunz, S. and Radbruch, H. and Chen, J. and Jüttner, R. and Kerkering, J. and Ucar, J. and Crowley, T. and Wielockx, B. and Paul, F. and Alisch, M. and Siffrin, V. |
| Abstract: | Astrocytes constitute the parenchymal border of the blood-brain barrier (BBB), modulate the exchange of soluble and cellular elements, and are essential for neuronal metabolic support. Thus, astrocytes critically influence neuronal network integrity. In hypoxia, astrocytes upregulate a transcriptional program that has been shown to boost neuroprotection in several models of neurological diseases. We investigated transgenic mice with astrocyte-specific activation of the hypoxia-response program by deleting the oxygen sensors, HIF prolyl-hydroxylase domains 2 and 3 (Phd2/3). We induced astrocytic Phd2/3 deletion after onset of clinical signs in experimental autoimmune encephalomyelitis (EAE) that led to an exacerbation of the disease mediated by massive immune cell infiltration. We found that Phd2/3-ko astrocytes, though expressing a neuroprotective signature, exhibited a gradual loss of gap-junctional Connexin-43 (Cx43), which was induced by vascular endothelial growth factor-alpha (Vegf-a) expression. These results provide mechanistic insights into astrocyte biology, their critical role in hypoxic states, and in chronic inflammatory CNS diseases. |
| Keywords: | Astrocyte, Experimental Autoimmune Encephalomyelitis, Hypoxia, Multiple Sclerosis, Neuroprotection, PHD2/PHD3, Animals, Mice |
| Source: | Glia |
| ISSN: | 0894-1491 |
| Publisher: | Wiley |
| Volume: | 71 |
| Number: | 8 |
| Page Range: | 2024-2044 |
| Date: | August 2023 |
| Official Publication: | https://doi.org/10.1002/glia.24380 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
Download Statistics
Download Statistics
