To study the regulation of adult neurogenesis and its relationship to behavior, we use rodents, mice and rats, which show features of adult neurogenesis nearly identical to those in primates, including regulation by stress and stress hormones. This year we published an investigation of the inhibition of adult neurogenesis in the dentate gyrus portion of the hippocampus by age. We previously found that glucocorticoids, or stress hormones, are responsible for the age-related decline in adult neurogenesis in the hippocampus; when glucocorticoids are removed from old rats by adrenalectomy, granule cell production returns to the relatively high levels seen in young adults. In the study published this year, we investigated how glucocorticoids in old age inhibit cell proliferation. We hypothesized that cell proliferation is slowed down by a slowing of the cell cycle, as occurs in development. However, we found that the cell cycle does not change during adulthood and that a loss of precursor cells is instead responsible for the generation of fewer new neurons. This finding is particularly intriguing, since we know that production of new neurons can be brought back to youthful levels, suggesting that new precursor cells can be added to the dentate gyrus in response to decreased glucocorticoid levels. We have also collaborated with SBSG (NIAAA) on two studies of stress effects on behavior. In the first, we found that chronic, but not acute, stress potentiates the sedative effects of alcohol, despite higher levels of glucocorticoids after acute stress. In the second, we examined a model of developmental stress, exposure to an unfamiliar adult male of the same species. This model has been well characterized in rats, but we found that in a commonly used strain of mice, exposure to an unfamiliar adult male produces no stress response in pups and no effect on the behavior of adult mice that were exposed to unfamiliar males as pups. This finding indicates that a new model will need to be developed in order to study the long-term effects of developmental stress using transgenic mouse lines.
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