| First Author | Le Moan N | Year | 2015 |
| Journal | eNeuro | Volume | 2 |
| Issue | 2 | PubMed ID | 26213713 |
| Mgi Jnum | J:229425 | Mgi Id | MGI:5751955 |
| Doi | 10.1523/ENEURO.0050-14.2015 | Citation | Le Moan N, et al. (2015) Hypoxia Inducible Factor-1 in Astrocytes and/or Myeloid Cells Is Not Required for the Development of Autoimmune Demyelinating Disease. eNeuro 2(2):e0050 |
| abstractText | Hypoxia-like tissue alterations, characterized by the upregulation of hypoxia-inducible factor-1alpha (HIF-1alpha), have been described in the normal appearing white matter and pre-demyelinating lesions of multiple sclerosis (MS) patients. As HIF-1alpha regulates the transcription of a wide set of genes involved in neuroprotection and neuroinflammation, HIF-1alpha expression may contribute to the pathogenesis of inflammatory demyelination. To test this hypothesis, we analyzed the effect of cell-specific genetic ablation or overexpression of HIF-1alpha on the onset and progression of experimental autoimmune encephalomyelitis (EAE), a mouse model for MS. HIF-1alpha was mainly expressed in astrocytes and microglia/macrophages in the mouse spinal cord at the peak of EAE. However, genetic ablation of HIF-1alpha in astrocytes and/or myeloid cells did not ameliorate clinical symptoms. Furthermore, conditional knock-out of Von Hippel Lindau, a negative regulator of HIF-1alpha stabilization, failed to exacerbate the clinical course of EAE. In accordance with clinical symptoms, genetic ablation or overexpression of HIF-1alpha did not change the extent of spinal cord inflammation and demyelination. Overall, our data indicate that despite dramatic upregulation of HIF-1alpha in astrocytes and myeloid cells in EAE, HIF-1alpha expression in these two cell types is not required for the development of inflammatory demyelination. Despite numerous reports indicating HIF-1alpha expression in glia, neurons, and inflammatory cells in the CNS of MS patients, the cell-specific contribution of HIF-1alpha to disease pathogenesis remains unclear. Here we show that although HIF-1alpha is dramatically upregulated in astrocytes and myeloid cells in EAE, cell-specific depletion of HIF-1alpha in these two cell types surprisingly does not affect the development of neuroinflammatory disease. Together with two recently published studies showing a role for oligodendrocyte-specific HIF-1alpha in myelination and T-cell-specific HIF-1alpha in EAE, our results demonstrate a tightly regulated cellular specificity for HIF-1alpha contribution in nervous system pathogenesis. |
