OVARIAN STEROID REGULATION OF SEROTONIN NEURAL FUNCTION

Oregon Health & Science University, Portland OR

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project examines the effect of estrogen (E) and progesterone (P) on serotonin neural function in macaques. Serotonin governs many autonomic and higher order neural functions. An elevation in serotonin neurotransmission is expected to benefit arousal, elevate mood and improve cognitive function. We are now pursing the hypothesis that ovarian hormones also improve serotonin neuron survival and serotonin neuronal plasticity. We determined the effect of ovarian steroid administration on gene expression related to dendritic spine protrusion in laser-captured serotonin neurons. We found that E[unreadable]P treatment for one month significantly increased gene expression for RhoA, Rac and cdc42 and their downstream effectors. These expression changes would increase spine proliferation on dendrites of serotonin neurons. Subsequently, we localized RhoA and cdc42 to the dorsal raphe region in the brain. We found that E+P significantly increased the cellular expression of RhoA and increased the dendritic staining of cdc42. We also completed behavioral studies of semi-free ranging Japanese macaques that were ovariectomized or tubal ligated for 3 years. The lack of ovarian steroids reduced serotonin production resulting in less success in navigating social situations and in anxiety-like behaviors that are manifested in isolated or stressful situations. In addition, we finished an exhaustive study of the CRF-UCN innervation and expression of CRF receptors in the dorsal raphe.