OVARIAN STEROID REGULATION OF SEROTONIN NEURAL FUNCTION

$140,736P51FY2009RRNIH

Oregon Health & Science University, Portland OR

Investigators

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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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. Neuroplasticity is manifested through a number of structural changes in the nervous system, but in the CNS, dendritic spines are the elementary structural units of neuronal plasticity. Dendritic spines exclusively express excitatory glutamate synapses and thereby increase stimulatory input to the respective neuron. Dendritic spines are protruded in a well-defined manner that involves the Rho GTPases, RhoA, Rac1 and cdc42. Rho GTPases control the polymerization, branching and bundling of actin, allowing them to regulate the remodeling of the actin cytoskeleton into distinct architectural elements. We determined the effect of ovarian steroid administration on gene expression of the Rho GTPases and members of their downstream signaling pathways in laser captured serotonin neurons. Ovariectomized (surgically menopausal) female rhesus monkeys were administered placebo, estrogen (E) or estrogen plus progesterone (E+P) for one month (n=3/group). The midbrain was sectioned at 7 [unreadable], immunostained for tryptophan hydroxylase (TPH) and identified neurons were captured using an Arcturus Laser Capture Microscope PixCell II.

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