Lack of 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 knock out (KO) mice were irradiated with 5 Gy and acute (8–48 hr) 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 non-irradiated 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. provides in hippocampal neurogenesis