Hypoxia suppresses neuronal functions in primary neuron, speeds cell cycle progression and affection the differentiation potential of neural stem cells

Multiple diseases are associated with a pathological hypoxia in the brain, resulting in various neurological sequalae. Understanding the response to hypoxia of neurons and neural stem cells (NSCs) will help devise better therapeutic strategies. We have exposed primary neurons (PN) and neural stem cells to 1% O2. Both cell types survived well, and neurons showed no obvious morphological changes. The NSCs, however, became fusiform, and displayed a population of cells with accelerated transition in cell cycle. Gene expression profile through microarray analysis revealed major differences in response to hypoxia between NSC and PN. Not only the number of genes significantly changes was ~five-fold higher in NSC, but the types of genes involved and the direction of change was quite different. In particular, NSCs up-regulated multiple growth factors and down-regulated most other cytokines and metalloproteases , while PN down-regulated most neuronal-specific genes, up-regulated growth factors, with no major effect on cytokines. We conclude that hypoxia 1- accelerates cell cycle transition of NSC in a post-transcriptional fashion ; 2-affects cytokines in NSC but not in neurons; 3-result in up-regulation of multiple growth factors in NSC and PN; and 4-suppresses neuronal specific functions.

9