Lack of extracellular superoxide dismutase (EC-SOD) in the microenvironment impacts radiation-induced changes in neurogenesis.
Ionizing irradiation results in significant alterations in hippocampal neurogenesis that are associated with cognitive impairments. Such effects are influenced, in part, by alterations in the microenvironment within which the neurogenic cells exist. One important factor that may affect neurogenesis is oxidative stress, and this study was done to determine if and how the extracellular isoform of superoxide dismutase (SOD3, EC-SOD) mediated radiation-induced alterations in neurogenic cells. Wild-type (WT) and EC-SOD knockout (KO) mice were irradiated with 5 Gy and acute (8-48 h) cellular changes and long-term changes in neurogenesis were quantified. Acute radiation responses were not different between genotypes, suggesting that the absence of EC-SOD did not influence mechanisms responsible for acute cell death after irradiation. On the other hand, the extent of neurogenesis was decreased by 39% in nonirradiated KO mice relative to WT controls. In contrast, while neurogenesis was decreased by nearly 85% in WT mice after irradiation, virtually no reduction in neurogenesis was observed in KO mice. These findings show that after irradiation, an environment lacking EC-SOD is much more permissive in the context of hippocampal neurogenesis. This finding may have a major impact in developing strategies to reduce cognitive impairment after cranial irradiation.
Rola
Radoslaw
R
Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94110-0899, and GRECC, VA Palo Alto Health Care System, USA.
Zou
Yani
Y
Huang
Ting-Ting
TT
Fishman
Kelly
K
Baure
Jennifer
J
Rosi
Susanna
S
Milliken
Heather
H
Limoli
Charles L
CL
Fike
John R
JR
D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology / Q000528:radiation effects; D003072:Cognition Disorders / Q000209:etiology*; D006624:Hippocampus / Q000201:enzymology / Q000528:radiation effects*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000201:enzymology; D009474:Neurons / Q000502:physiology / Q000528:radiation effects*; D018384:Oxidative Stress; D011839:Radiation, Ionizing; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1
C000606291:Sod1 protein, mouse; C499090:Sod3 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1