title: Proliferative neural stem cells have high endogenous ROS levels that regulate self-renewal and neurogenesis in a PI3K/Akt-dependant manner.
abstract: The majority of research on reactive oxygen species (ROS) has focused on their cellular toxicities. Stem cells generally have been thought to maintain low levels of ROS as a protection against these processes. However, recent studies suggest that ROS can also play roles as second messengers, activating normal cellular processes. Here, we investigated ROS function in primary brain-derived neural progenitors. Somewhat surprisingly, we found that proliferative, self-renewing multipotent neural progenitors with the phenotypic characteristics of neural stem cells (NSC) maintained a high ROS status and were highly responsive to ROS stimulation. ROS-mediated enhancements in self-renewal and neurogenesis were dependent on PI3K/Akt signaling. Pharmacological or genetic manipulations that diminished cellular ROS levels also interfered with normal NSC and/or multipotent progenitor function both in vitro and in vivo. This study has identified a redox-mediated regulatory mechanism of NSC function that may have significant implications for brain injury, disease, and repair.
authors.affiliation: NPI-Semel Institute for Neuroscience & Human Behavior and Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Janel E
authors.initials: JE
authors.lastname: Le Belle
authors.forename: Nicolas M
authors.initials: NM
authors.lastname: Orozco
authors.forename: Andres A
authors.initials: AA
authors.lastname: Paucar
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Saxe
authors.forename: Jack
authors.initials: J
authors.lastname: Mottahedeh
authors.forename: April D
authors.initials: AD
authors.lastname: Pyle
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Harley I
authors.initials: HI
authors.lastname: Kornblum
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt