All ETDs from UAB

Advisory Committee Chair

Lori L McMahon

Advisory Committee Members

Rita Cowell

David Knight

Xiaohua Li

Michael Sloane

Diane Tucker

Document Type

Dissertation

Date of Award

2011

Degree Name by School

Doctor of Philosophy (PhD) College of Arts and Sciences

Abstract

A recent focus of psychiatric research is estrogen related mood disorders such as postpartum depression and major depressive disorder in women. It is now clear that women are more susceptible to depression in response to stress during reproductive events when ovarian hormones are low or fluctuating. Depressive episodes are characterized by feelings of helplessness and despair as well as learning and memory impairments that have been linked to the hippocampus. Thus, decreased functioning of hippocampal circuits likely contributes to the cognitive symptoms associated with depression. Preclinical research shows that stress, which triggers depressive episodes, decreases the ability of excitatory synapses in hippocampus to express long-term potentiation (LTP), a cellular correlate of learning and memory. It is also well known that estrogen (17ß estradiol; E2) has protective effects in hippocampus, leading to increased synapse density, enhanced LTP, and improved memory. Because the beneficial effects of estrogen are in opposition to the harmful consequences of stress, we hypothesize that hormonal fluctuations in women could leave hippocampal circuits vulnerable to the detrimental effects of stress and increase susceptibility to depression. Using the Learned Helpless (LH) model of depression in animals, we examined the role of E2 in the expression of LH and how this behavior affects synaptic plasticity in the hippocampus. We found that ovariectomized rats treated with proestrus levels of E2 were less likely to acquire LH and that E2 treatment reverses previously established LH. Moreover, hippocampal slices from E2 treated animals exposed to LH training and testing demonstrated an increased magnitude of long term potentiation (LTP) at CA3-CA1 synapses that was not found in vehicle treated controls. These results indicate that E2 decreases stress reactivity in rats subjected to inescapable shock in LH and that the beneficial effects of E2 on hippocampal synaptic physiology may protect against hippocampal related cognitive deficits associated with depression-like behavior. Thus, we conclude that E2 therapy in women may provide protection against the development of depression or serve to reverse depressive behavior associated with alterations in ovarian hormone levels.

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