Radiation-induced reductions in neurogenesis are ameliorated in mice deficient in CuZnSOD or MnSOD.
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.
Fishman
Kelly
K
Department of Neurological Surgery, University of California at San Francisco, San Francisco, CA 94110-0899, USA.
Baure
Jennifer
J
Zou
Yani
Y
Huang
Ting-Ting
TT
Andres-Mach
Marta
M
Rola
Radoslaw
R
Suarez
Tatiana
T
Acharya
Munjal
M
Limoli
Charles L
CL
Lamborn
Kathleen R
KR
Fike
John R
JR
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
D013482:Superoxide Dismutase
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