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ESTROGEN, PROGESTERONE AND BDNF INTERACTIONS:
ROLES IN NEUROPROTECTION
by
Claudia C. Aguirre
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(NEUROSCIENCE)
December 2009
Copyright 2009 Claudia C. Aguirre
Object Description
| Title | Estrogen, progesterone and BDNF interactions: roles in neuroprotection |
| Author | Aguirre, Claudia C. |
| Author email | bellestar1@gmail.com; ccaguirr@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Neuroscience |
| School | College of Letters, Arts and Sciences |
| Date defended/completed | 2009-08-27 |
| Date submitted | 2009 |
| Restricted until | Unrestricted |
| Date published | 2009-11-06 |
| Advisor (committee chair) | Baudry, Michel |
| Advisor (committee member) |
Thompson, Richard Madigan, Stephen |
| Abstract | Human cognition encompasses all the components involved in information processing. Thus, it is a multidimensional concept that involves several aspects of learning, memory, abstract reasoning and other higher-order functions. Interest in hormone effects on memory mechanisms has been spurred by conflicting evidence implicating that hormone replacement therapy (HT) can ameliorate or be detrimental to memory and cognitive ability in post-menopausal women. The functions of the female gonadal steroids estrogen and progesterone in the central nervous system (CNS) have been extensively studied. One of the regions involving estrogenic action most studied is the hippocampal formation, which governs the formation of spatial and episodic memories. Relatively less attention has been devoted to progesterone (P4) and its effects in hippocampus. Moreover, the possible regulation by P4 of E2-mediated neuroprotective effects has not been extensively investigated. This dissertation is directed at studying interactions between estrogen and progesterone in an in-vitro model of excitotoxicity, and at evaluating the role of brain-derived neurotrophic factor (BDNF) in mediating estradiol-induced neuroprotection, using NMDA treatment of cultured hippocampal slices to elicit neuronal death. I hypothesized that the neuroprotective effects of these hormones was critically dependent upon the timing of hormone administration. Further, I proposed that estrogenic neuroprotection against NMDA toxicity was dependent on the activation of BDNF and its resulting signaling pathways, an effect mediated through the ERbeta receptor. Using organotypic hippocampal slices, we showed that treatment with estradiol paired with progesterone resulted in down-regulation of ERbeta mRNA leading to diminished ERbeta-mediated estradiol responses, and in particular, in decreased BDNF expression and protein levels, which accounted for elimination of estrogen protection against NMDA toxicity.; A better understanding of the role of the temporal order of treatment with gonadal steroid hormones on neurotrophin regulation may provide insight into the role of these hormones as neuroprotective agents in neurological disorders such as Alzheimer's and Parkinson's disease and as potential therapeutic treatments. |
| Keyword | estrogen; progesterone; BDNF; hippocampus; Alzheimer's disease; estrogen receptor beta; NMDA; neuroprotection; organotypic hippocampal slice |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m2717 |
| Rights | Aguirre, Claudia C. |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Aguirre-3192 |
| Archival file | uscthesesreloadpub_Volume44/etd-Aguirre-3192.pdf |
Description
| Title | Page 1 |
| Full text | ESTROGEN, PROGESTERONE AND BDNF INTERACTIONS: ROLES IN NEUROPROTECTION by Claudia C. Aguirre A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (NEUROSCIENCE) December 2009 Copyright 2009 Claudia C. Aguirre |
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