| First Author | Carrica L | Year | 2019 |
| Journal | Neurobiol Learn Mem | Volume | 157 |
| Pages | 79-85 | PubMed ID | 30521851 |
| Mgi Jnum | J:295119 | Mgi Id | MGI:6459661 |
| Doi | 10.1016/j.nlm.2018.12.002 | Citation | Carrica L, et al. (2019) Genetic inactivation of hypoxia inducible factor 1-alpha (HIF-1alpha) in adult hippocampal progenitors impairs neurogenesis and pattern discrimination learning. Neurobiol Learn Mem 157:79-85 |
| abstractText | HIF-1alpha is a hypoxia-inducible protein that regulates many cellular processes, including neural stem cell maintenance. Previous work demonstrated constitutive stabilization of HIF-1alpha in neural stem cells (NSCs) of the adult mouse subventricular zone (SVZ) and hippocampal subgranular zone (SGZ). Genetic inactivation of NSC-encoded HIF-1alpha in the adult SVZ results in gradual loss of NSCs, but whether HIF-1alpha is required for the maintenance of SGZ hippocampal progenitors and adult hippocampal neurogenesis has not been determined. Here we tested the hypothesis that HIF-1alpha plays an essential role in the maintenance of adult hippocampal neurogenesis using Nestin-CreER(T2)/R26R-YFP/Hif1a(fl/fl) triple transgenic mice, in which HIF-1alpha was genetically inactivated in nestin(+) hippocampal progenitors and their downstream progeny following tamoxifen exposure. We found that disruption of HIF-1alpha gene expression resulted in a marked 50% reduction of adult-generated dentate granule cells (DGCs) that was highly correlated with impaired hippocampal function, as assessed using two behavioral assays of pattern discrimination. These behavioral tests included the A-B contextual fear-conditioning task and the trial-unique, delayed nonmatching-to-location (TUNL) touch-screen operant chamber task. Our findings identify HIF-1alpha as a novel regulator of adult hippocampal neurogenesis under non-pathological conditions, and underscore the importance of neurogenesis for pattern discrimination learning. |
