title: Radiation-induced reductions in neurogenesis are ameliorated in mice deficient in CuZnSOD or MnSOD.
abstract: Ionizing irradiation significantly affects hippocampal neurogenesis and is associated with cognitive impairments; these effects may be influenced by an altered microenvironment. Oxidative stress is a factor that has been shown to affect neurogenesis, and one of the protective pathways that deal with such stress involves the antioxidant enzyme superoxide dismutase (SOD). This study addressed what impact a deficiency in cytoplasmic (SOD1) or mitochondrial (SOD2) SOD has on radiation effects on hippocampal neurogenesis. Wild-type (WT) and SOD1 and SOD2 knockout (KO) mice received a single X-ray dose of 5 Gy, and quantification of the survival and phenotypic fate of newly generated cells in the dentate subgranular zone was performed 2 months later. Radiation exposure reduced neurogenesis in WT mice but had no apparent effect in KO mice, although baseline levels of neurogenesis were reduced in both SOD KO strains before irradiation. Additionally, there were marked and significant differences between WT and both KO strains in how irradiation affected newly generated astrocytes and activated microglia. The mechanism(s) responsible for these effects is not yet known, but a pilot in vitro study suggests a "protective" effect of elevated levels of superoxide. Overall, these data suggest that under conditions of SOD deficiency, there is a common pathway dictating how neurogenesis is affected by ionizing irradiation.
authors.affiliation: Department of Neurological Surgery, University of California at San Francisco, San Francisco, CA 94110-0899, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Fishman
authors.forename: Jennifer
authors.initials: J
authors.lastname: Baure
authors.forename: Yani
authors.initials: Y
authors.lastname: Zou
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Huang
authors.forename: Marta
authors.initials: M
authors.lastname: Andres-Mach
authors.forename: Radoslaw
authors.initials: R
authors.lastname: Rola
authors.forename: Tatiana
authors.initials: T
authors.lastname: Suarez
authors.forename: Munjal
authors.initials: M
authors.lastname: Acharya
authors.forename: Charles L
authors.initials: CL
authors.lastname: Limoli
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Lamborn
authors.forename: John R
authors.initials: JR
authors.lastname: Fike
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D006579:Heterozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055495:Neurogenesis / Q000528:radiation effects*; D009474:Neurons / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism / Q000528:radiation effects*; D018384:Oxidative Stress; D011839:Radiation, Ionizing; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000378:metabolism
chemical_list: D013482:Superoxide Dismutase
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