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| Content Provider | Springer Nature Link |
|---|---|
| Author | Genetos, Damian C. Cheung, Whitney K. Decaris, Martin L. Leach, J. Kent |
| Copyright Year | 2010 |
| Abstract | Cell-based approaches are a promising therapeutic strategy for treating injuries to the nervous system, but the optimal means to promote neurite extension and direct cellular behavior are unclear. Previous studies have examined the behavior of neural-like cells in ambient air (21% oxygen tension), yet these conditions are not representative of the physiological oxygen microenvironment of neural tissues. We hypothesized that neuronal differentiation of a model neural cell line (PC12) could be controlled by modulating local oxygen tension. Compared to ambient conditions, PC12 cells cultured in reduced oxygen exhibited significant increases in neurite extension and total neurite length, with 4% oxygen yielding the highest levels of both indicators. We confirmed neurite extension was mediated through oxygen-responsive mechanisms using small molecules that promote or inhibit HIF-1α stabilization. The hypoxic target gene Vegf was implicated as a neurotrophic factor, as neurite formation at 21% oxygen was mimicked with exogenous VEGF, and a VEGF-neutralizing antibody attenuated neurite formation under reduced oxygen conditions. These findings demonstrate that behavior of neural-like cells is driven by the oxygen microenvironment via VEGF function, and suggest promising approaches for future applications in neural repair. |
| Starting Page | 360 |
| Ending Page | 366 |
| Page Count | 7 |
| File Format | |
| ISSN | 08958696 |
| Journal | Journal of Molecular Neuroscience |
| Volume Number | 40 |
| Issue Number | 3 |
| e-ISSN | 15591166 |
| Language | English |
| Publisher | Humana Press Inc |
| Publisher Date | 2010-01-27 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Oxygen tension Neurite extension PC12 Hypoxia-inducible factor Vascular endothelial growth factor Neurology Neurosciences |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Cellular and Molecular Neuroscience |
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