The objective of the proposed research is to determine the effects of lone-term estrogen treatment on the structure of individual neurons in the mammalian brain. Although estrogen improves memory and reduces the risk of developing Alzheimer's disease in post-menopausal women. and improves performance on certain learning and memory tasks in rodents, its effects on individual cortical neurons are not yet understood. Recent evidence indicates that short-term estrogen treatment causes structural changes in cortical neurons. The effects of long-term estrogen treatment. however. on the dendritic structure of neurons in the brain have not been examined. The first specific aim is to test the hypothesis that long-term estrogen treatment affects the structure of neurons in the hippocampal formation of young adult and aged female rats. The hippocampal formation is crucial for certain forms of learning and memory in humans and rodents. The second specific aim is to test the hypothesis that structural changes following estrogen treatment correlate with performance on a learning and memory task known to be mediated by the hippocampal formation. To accomplish specific aim 1, young adult and aged female rats will be ovariectomized. and a subgroup of each age group will be treated with estrogen. The structure of neurons in the hippocampal formation of the ovariectomized, estrogen-treated, and control animals will be quantified and compared between groups. To accomplish specific aim 2, the learning abilities of animals in the groups under specific aim I will be tested on a task known to be mediated by the hippocampus, and the behavioral data wil l be correlated with the structural data. Results will indicate whether or not long-term estrogen treatment causes structural changes in hippocampal neurons. and whether or not such changes correlate with performance on a learning and memory task. Given the wide-spread clinical use of Estrogen Replacement Therapy and its known cognitive effects, it is imperative that we develop an understanding of the effects of long-term estrogen treatment on neurons in the mammalian brain. It will not be possible to develop equivalent, non-steroidal therapies for memory impairments in postmenopausal %women, or in aged men, until the underlying cellular mechanisms of estrogen's cognitive effects are elucidated.
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