21522-21527 | PNAS | December 26, 2012 | vol. 109 | no. 52

Extracellular superoxide dismutase is important for hippocampal neurogenesis and preservation of cognitive functions after irradiation.

Yani Zoua, Rikki Corniolaa, David Leua,b, Aslam Khana,b, Peyman Sahbaiec,d, Ayanabha Chakrabortie, David J. Clarkc,d, John R. Fikee,f, and Ting-Ting Huanga,b,1

aDepartment of Neurology and Neurological Sciences and dDepartment of Anesthesia, Stanford University, Stanford, CA 94304; bGeriatric Research, Education and Clinical Center, and cAnesthesiology Service, Veteran’s Affairs Palo Alto Health Care System, Palo Alto, CA 94304; and eDepartment of Neurological Surgery and fDepartment of Radiation Oncology, University of California, San Francisco, CA 94143

Hippocampus plays an important role in learning and memory and in in spatial navigation. Production of new neurons that are functionally integrated into the hippocampal neuronal networks is important for maintenance of functional plasticity. Cranial irradiation is widely used as treatment modality for primary or brain metastatic tumors patient, but it often causes cognitive defect in cancer survivors. Oxidative stress is considered a major cause of tissue injury from irradiation. Earlier study mice deficient in the antioxidant enzyme extracellular superoxide dismutase (EC-SOD KO) showed reduced sensitivity to radiation- induced defects in hippocampal functions.

 In this study they showed that EC-SOD deficiency had a negative impact on progenitor cell proliferation on longtime survival of newborn neurons in dentate gyrus of hippocampus,   high levels of EC-SOD in granule cells supported dendritic development and long term survival of newborn neurons, compared with wild type mice, over expression (OE) mice and knockout (KO) mice were less sensitive to irradiation-induced changes in hippocampal neurogenesis and the associated cognitive functions, and neurotropic factors and molecules controlling axon/dendrite maintenance were differentially affected by EC-SOD levels and irradiation.