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PROGESTERONE RECEPTORS IN THE RAT BRAIN AND THEIR ROLE IN STEROIDAL REGULATION OF NEURITE OUTGROWTH
by
Namrata Bali
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
(MOLECULAR BIOLOGY)
August 2012
Copyright 2012 Namrata Bali
Object Description
| Title | Progesterone receptors in the rat brain and their role in steroidal regulation of neurite outgrowth |
| Author | Bali, Namrata |
| Author email | nbali@usc.edu;nbali.usc.ca@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Molecular Biology |
| School | College of Letters, Arts And Sciences |
| Date defended/completed | 2012-06-04 |
| Date submitted | 2012-06-20 |
| Date approved | 2012-06-20 |
| Restricted until | 2012-06-20 |
| Date published | 2012-06-20 |
| Advisor (committee chair) | Finch, Caleb E. |
| Advisor (committee member) |
Tower, John G. Schauwecker, P. Elyse |
| Abstract | Estrogen (E2) and progesterone (P4) regulate synaptic plasticity in the adult rat hippocampus during the normal rat estrous cycle and in response to deafferenting lesions. E2 increases neurite sprouting, whereas P4 antagonizes the E2-induced neurite outgrowth. Moreover, in the in vitro wounding-in-a-dish lesion model with glia-neuron co-cultures, E2 increases neurite outgrowth and P4 antagonizes the E2-induced neurite outgrowth. However, the P4-E2 antagonism of neurite outgrowth was only seen in the presence of microglia. The receptors involved in the P4 responses to neurite outgrowth are not well understood. Two progesterone mediators, Pgrmc1 and Pgr are studied in this thesis. ❧ Both Pgrmc1 and Pgr are expressed in the CA1, CA3 and DG hippocampal neurons, although their expression patterns differ between the neuronal subtypes. Both Pgrmc1 and Pgr are also regulated by E2 and P4 in the hippocampal neurons. Pgrmc1 mRNA is upregulated by both E2 and P4 in CA1, CA3 and DG neurons, while Pgr is hormonally regulated in CA1 neurons only. The differential expression and regulation of Pgrmc1 and Pgr in different hippocampal neurons could be due to possible different functions mediated by each in the different neurons. Pgrmc1 and Pgr are also expressed in glia. While both are expressed in astrocytes, only Pgrmc1 is expressed in microglia. ❧ Using a new microglia add-back protocol, microglia are shown to be required for P4-E2 antagonism of neurite outgrowth. However, physical contact between microglia and neurons is not required for the P4 antagonism, and soluble factors from activated microglia suffice to restore P4-E2 antagonism. Moreover, Pgrmc1 expression in microglia is required for the P4-E2 antagonism of neurite outgrowth. ❧ These findings together provide evidence of a P4 mediator in microglia with novel roles in P4 regulation of neurite outgrowth and in regulation of microglial activation. Understanding the mechanisms involved in P4-E2 regulation of synaptic plasticity is important in optimization of postmenopausal hormone therapy and in the therapeutic use of P4 for traumatic brain injury. |
| Keyword | microglia; Pgrmc1; progesterone; neurite outgrowth; progesterone receptor |
| 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-m |
| Contributing entity | University of Southern California |
| Rights | Bali, Namrata |
| Physical access | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@lib.usc.edu |
| Archival file | uscthesesreloadpub_Volume4/etd-BaliNamrat-895.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | PROGESTERONE RECEPTORS IN THE RAT BRAIN AND THEIR ROLE IN STEROIDAL REGULATION OF NEURITE OUTGROWTH by Namrata Bali 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 (MOLECULAR BIOLOGY) August 2012 Copyright 2012 Namrata Bali |
