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Degree

PhD, University of Cincinnati, Medicine : Neuroscience/Medical Science Scholars Interdisiplinary, 2008.

Abstract

The hypothalamus-pituitary-adrenal (HPA) axis is the main neuroendocrine arm of the stress response, activation of which leads to the production of glucocorticoid hormones. Glucocorticoids are steroid hormones that are secreted from the adrenal cortex, and have a variety of effects on the body, including modulation of the immune system, suppression of reproductive hormones, and maintenance of blood glucose levels, and maintenance of blood pressure. Activity of the HPA axis is known to be modulated by signaling through molecules like glutamate and glucocorticoids. Although it is clear that these signals play a role in HPA axis regulation, their roles in regulating the HPA axis at the paraventricular nucleus of the hypothalamus (PVN) are not yet entirely clear. In this work, we demonstrate HPA regulatory roles for the ionotropic glutamate receptor GluR5, the group I metabotropic glutamate receptors, and glucocorticoids at the PVN. GluR5 inhibits the HPA axis response to restraint stress when acting near the cell bodies in the PVN proper, and plays an excitatory role at axon terminals in the median eminence. Group I metabotropic glutamate receptor signaling has an inhibitory effect on the HPA axis response to restraint stress at the PVN. Glucocorticoids also exert an inhibitory influence on HPA axis activity at the level of the PVN. This negative regulation of the HPA axis by glucocorticoids is likely nongenomic in nature and occurs on a very rapid time scale. This fast feedback is mediated by cannabinoid CB1 receptor signaling at the PVN. Thus, glutamate and glucocorticoids acting at the PVN can inhibit the HPA axis response to restraint stress in rats.

Subject Headings

Neurology

Keywords

HPA axis; glutamate; cannabinoids; nongenomic; glucocorticoids

Committee / Advisors

James Herman, PhD (Committee Chair)
Randall Sakai, PhD (Committee Member)
Stephen Woods, PhD (Committee Member)
David D'Alessio, MD (Committee Member)
Yvonne Ulrich-Lai, PhD (Committee Member)

Pages

168p.

Document number: ucin1227289026
Permalink: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1227289026

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