HORMONAL INTERACTION WITH AGING BRAIN

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As the proportion of post-menopausal women in the population has increased, hormone replacement has become increasingly commonplace. Recently, research has suggested that estrogens and progestins can affect higher order, cognitive behaviors when used in replacement after menopause and in their fluctuations during the menstrual cycle. Estrogens also appear to delay the onset of Alzheimer's disease, as well as modulate schizophrenic symptoms. An animal model of these effects would be useful in understanding how the ovarian steroids influence parts of the nervous system dealing with higher cognitive functions through the lifespan. The long term goal of this research is to explore the effects of ovarian steroids on cognitive behavior and concomitant neural substrates in the cycling and aging female rat. Before commencing on large and detailed studies with hormone manipulations, preliminary data are sought to select which neural area upon which to concentrate. The effects of the estropausal state of the aging rat and the phase of the cycle in young adult females on spine densities and dendritic field extent will be examined. Two cognitively relevant areas will be sampled: the hippocampus and the medial prefrontal cortex. There is preliminary data that spine densities drop precipitously with age (28-40 percent) in the medial prefrontal cortex. If this area is sensitive to ovarian hormones in aging, it would be an excellent model for age related changes in female anatomy and behavior. If it is relatively refractory to ovarian steroids, changes in the medial prefrontal cortex would be a useful model for general aging effects in both sexes.