Present Address: Department of Neurosurgery, University of Florida, Gainesville, Florida 32610.
Neural stem/progenitor cells display a low requirement for oxidative metabolism independent of hypoxia inducible factor-1alpha expression
Article first published online: 11 MAR 2013
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 125, Issue 3, pages 420–429, May 2013
How to Cite
J. Neurochem.(2013) 125, 420–429.
- Issue published online: 21 APR 2013
- Article first published online: 11 MAR 2013
- Accepted manuscript online: 15 FEB 2013 03:01AM EST
- Manuscript Accepted: 4 FEB 2013
- Manuscript Revised: 29 JAN 2013
- Manuscript Received: 18 SEP 2012
- neural progenitor cell;
- neural stem cell
Neural stem/progenitor cells (NSPCs) are multipotent cells within the embryonic and adult brain that give rise to both neuronal and glial cell lineages. Maintenance of NSPC multipotency is promoted by low oxygen tension, although the metabolic underpinnings of this trait have not been described. In this study, we investigated the metabolic state of undifferentiated NSPCs in culture, and tested their relative reliance on oxidative versus glycolytic metabolism for survival, as well as their dependence on hypoxia inducible factor-1alpha (HIF-1α) expression for maintenance of metabolic phenotype. Unlike primary neurons, NSPCs from embryonic and adult mice survived prolonged hypoxia in culture. In addition, NSPCs displayed greater susceptibility to glycolytic inhibition compared with primary neurons, even in the presence of alternative mitochondrial TCA substrates. NSPCs were also more resistant than neurons to mitochondrial cyanide toxicity, less capable of utilizing galactose as an alternative substrate to glucose, and more susceptible to pharmacological inhibition of the pentose phosphate pathway by 6-aminonicotinamide. Inducible deletion of exon 1 of the Hif1a gene improved the ability of NSPCs to utilize pyruvate during glycolytic inhibition, but did not alter other parameters of metabolism, including their ability to withstand prolonged hypoxia. Taken together, these data indicate that NSPCs have a relatively low requirement for oxidative metabolism for their survival and that hypoxic resistance is not dependent upon HIF-1α signaling.