Chronic Oral Estrogen Affects Memory and Neurochemistry in Middle-Aged Female Mice.

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Abstract
This study tested whether chronic oral estrogen could improve memory and alter neural plasticity in the hippocampus and neocortex of middle-aged female mice. Ovariectomized C57BL/6 mice were administered 1,000, 1,500, or 2,500 nM 17beta-estradiol in drinking water for 5 weeks prior to and during spatial and object memory testing. Synaptophysin, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) levels were then measured in hippocampus and neocortex. The medium dose impaired spatial reference memory in the radial-arm maze, whereas all doses improved object recognition. The high dose increased hippocampal synaptophysin and NGF levels, whereas the medium dose decreased these neocortical levels. The high dose decreased neocortical BDNF levels. These data suggest that chronic oral estrogen selectively affects memory and neural function in middle-aged female mice.