A research group led by Professor Yusaku Nakabetsu of the Institute of Biodefense Medicine, Kyushu University, discovered that the accumulation of oxidized nucleotides by active oxygen affects the gender difference in mouse behavior.
There are gender differences in animal brain function and behavior, but the mechanism is not well understood.This time, the research group is a wild-type TO-DKO mouse that lacks both 8-oxo-dGTP-degrading enzyme (MTH8) and 1-oxoG DNA glycosylase (OGG8), which prevent the accumulation of 1-oxoG oxidizing base in the genome. Using mice, the effects of aging on their behavior and cognitive function were compared and analyzed in male and female mice.
As a result, in wild-type mice, females showed about twice as much locomotor activity as males, and both male and female mice showed a decrease in activity with aging.However, in TO-DKO female mice, locomotor activity remains at a high level even in middle and old age, and when MTH1 and OGG1 are deficient, the nuclear genome of the neural progenitor cells of the hippocampus and subventricular zone only in female mice. It was discovered that 8-oxoG was accumulated in the hippocampus and that neoplastic nerve cells fell into apoptosis.Furthermore, in TO-DKO female mice, a specific part of the brain that suppresses locomotor activity is markedly atrophied and the locomotor activity is maintained at a high level, and in TO-DKO female mice, the hippocampal dentate gyrus is also atrophied. It was found that mild cognitive dysfunction was observed.
It is known that females have a higher incidence of depression and Alzheimer's disease than males, and one of the reasons is suggested to be oxidative damage to the genome and the involvement of its repair / defense system.From this finding, it is expected to develop preventive and therapeutic methods for diseases that focus on gender differences.
