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Submitted on February 18, 2003
Accepted on August 7, 2003
1 Center for Reproductive Medicine and Infertility, Weill Medical College of Cornell University, New York, NY 10021; Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10021; Department of Psychology, University of California Santa Barbara, Santa Barbara, CA 93106; Divisions of Reproductive Sciences and Neuroscience, Oregon National Primate Research Center, Beaverton, OR 97006
* To whom correspondence should be addressed. E-mail: mcewen{at}rockefeller.edu.
The role of estrogen in promoting learning and memory in females has been well studied in both rodent and primate models. In female rats, estrogen increases dendritic spine number, synaptogensis, and synaptic proteins in the CA1 region of the hippocampus, an area of the brain that mediates learning and memory. In the present study we used radioimmunocytochemistry to examine whether estrogen and progesterone were capable of modulating the levels of pre- and post-synaptic proteins in the CA1 region of the female nonhuman primate hippocampus. It was found that estrogen increased syntaxin, synaptophysin (presynaptic), and spinophilin (postsynaptic) levels in the stratum oriens and radiatum of the CA1 region, while combined estrogen and progesterone treatment decreased these synaptic proteins to the levels found in untreated, spay controls. Furthermore, progesterone treatment alone significantly increased synaptophysin levels in the stratum oriens and radiatum of the CA1 region. The levels of these synaptic proteins were unaltered by hormone treatment in the dentate gyrus suggesting this steroid-induced plasticity is hippocampal region specific. As these synaptic proteins are important components of the synaptic apparatus and reliable markers of synaptogensis, it appears that estrogen-induced increases in cognitive function of higher order mammals may be mediated in part by the effect of estrogen on hippocampal synaptogenesis and synaptic plasticity.
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