Oxidative stress and redox regulation on hippocampal-dependent cognitive functions.

Hippocampal-dependent cognitive functions rely on production of new neurons and maintenance of dendritic structures to provide the synaptic plasticity needed for learning and formation of new memories. Hippocampal formation is exquisitely sensitive to patho-physiological changes, and reduced antioxidant capacity and exposure to low dose irradiation can significantly impede hippocampal-dependent functions of learning and memory by reducing the production of new neurons and alter dendritic structures in the hippocampus. Although the mechanism leading to impaired cognitive functions is complex, persistent oxidative stress likely plays an important role in the SOD-deficient and radiation-exposed hippocampal environment. Aging is associated with increased production of pro-oxidants and accumulation of oxidative end products. Similar to the hippocampal defects observed in SOD-deficient mice and mice exposed to low dose irradiation, reduced capacity in learning and memory, diminishing hippocampal neurogenesis, and altered dendritic network are universal in the aging brains. Given the similarities in cellular and structural changes in the aged, SOD-deficient, and radiation-exposed hippocampal environment and the corresponding changes in cognitive decline, understanding the shared underlying mechanism will provide more flexible and efficient use of SOD deficiency or irradiation to model age-related changes in cognitive functions and identify potential therapeutic or intervention methods.