title: Localized hypoxia within the subgranular zone determines the early survival of newborn hippocampal granule cells.
abstract: The majority of adult hippocampal newborn cells die during early differentiation from intermediate progenitors (IPCs) to immature neurons. Neural stem cells in vivo are located in a relative hypoxic environment, and hypoxia enhances their survival, proliferation and stemness in vitro. Thus, we hypothesized that migration of IPCs away from hypoxic zones within the SGZ might result in oxidative damage, thus triggering cell death. Hypoxic niches were observed along the SGZ, composed of adult NSCs and early IPCs, and oxidative byproducts were present in adjacent late IPCs and neuroblasts. Stabilizing hypoxia inducible factor-1α with dimethyloxallyl glycine increased early survival, but not proliferation or differentiation, in neurospheres in vitro and in newly born SGZ cells in vivo. Rescue experiments in Bax(fl/fl) mutants supported these results. We propose that localized hypoxia within the SGZ contributes to the neurogenic microenvironment and determines the early, activity-independent survival of adult hippocampal newborn cells.
authors.affiliation: The Vollum Institute, Oregon Health and Science University, Portland, United States.
authors.forename: Christina
authors.initials: C
authors.lastname: Chatzi
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, United States.|United States Department of Veterans Affairs, VA Portland Health Care System, Portland, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Schnell
authors.affiliation: The Vollum Institute, Oregon Health and Science University, Portland, United States.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Westbrook
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D006624:Hippocampus / Q000254:growth & development / Q000502:physiology*; D000860:Hypoxia; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000502:physiology*
keywords: adult neurogenesis; hypoxia; mouse; neuroscience; survival