A variety of studies show that estrogen may promote memory in females, both animal and human with low estrogen levels. Moreover, estrogen may also delay or prevent the onset of Alzheimer's Disease and improve cognition in women with the disease. Using young and aged rats as models, experiments will examine effects of gonadal hormones on memory using a spatial memory task, object recognition. First, the dose- response relationship between estrogen and enhanced memory will be determined.. Whether concurrent administration of progesterone with estrogen alters the enhancing effects of estrogen on memory will be tested. Then possible enduring effects of gonadal hormones on memory will be tested, i.e., whether chronic estrogen alone or with progesterone enhances memory months after discontinuation. Effects of these hormone treatments on GABAergic and monoaminergic neurotransmission in brain areas involved in memory function will be measured by neurochemical techniques. Whether alterations in memory occur over the estrus cycle and after chronic ovariectomy will be determined and will show whether hormones exert short term effects or long term, trophic effects. Thus, proposed experiments will characterized fundamental relationships between gonadal hormones and memory function. While important for providing basic information concerning hormone actions and the neural bases for hormonal effects on memory, the studies also have significant health implications for aging and Alzheimer's disease. Concurrent estrogen and progesterone therapy is the treatment of choice for post menopausal women, but little is known about the effects of progesterone on memory. In addition, if post-menopausal hormone replacement therapy can delay dementia onset by 5 years, the incidence of dementia has been projected to decreased by 50%. Finally, if only a few years of replacement can be given with the same benefits on memory loss or in developing AD, then the risk of side effects of estrogen can be greatly minimized.
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