Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 47, Issue 10, Pages 1459-1467Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2009.08.016
Keywords
Radiation; Brain; Neurogenesis; Oxidative stress; inflammation; SOD; Free radicals
Funding
- NIH [R01 NS46051, AG24400]
- NSCOR [NNJ04HC90G]
- VA Palo Alto Health Care System
- Palo Alto Institute for Research and Education
- ACS [RSG-00-036-04-CNE]
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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. (C) 2009 Elsevier Inc. All rights reserved
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