Page 1 |
Save page Remove page | Previous | 1 of 211 | Next |
|
small (250x250 max)
medium (500x500 max)
large ( > 500x500)
Full Resolution
All (PDF)
|
This page
All
Subset |
ESTROGEN AND PROGESTERONE INTERACTIONS IN NEURONS:
IMPLICATIONS FOR ALZHEIMER’S DISEASE-RELATED PATHWAYS
By
Anusha Jayaraman
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)
August 2010
Copyright 2010 Anusha Jayaraman
Object Description
| Title | Estrogen and progesterone interactions in neurons: implications for Alzheimer's disease-related pathways |
| Author | Jayaraman, Anusha |
| Author email | anujay.ganguly@gmail.com; ajayaram@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Neuroscience |
| School | College of Letters, Arts and Sciences |
| Date defended/completed | 2010-06-14 |
| Date submitted | 2010 |
| Restricted until | Unrestricted |
| Date published | 2010-08-05 |
| Advisor (committee chair) | Pike, Christian J. |
| Advisor (committee member) |
Brinton, Roberta D. Baudry, Michel Rayudu, Gopalakrishna |
| Abstract | The depletion of estrogen and progesterone in postmenopausal women is associated with increased risk for several disorders in the cardiovascular, skeletal and nervous system. To reduce this risk, hormone therapy containing estrogens and a synthetic progestagen has been used but with little success. For example, the Women’s Health Initiative clinical trial showed that hormone therapy was associated with reduced incidence of hip fractures associated with osteoporosis but unexpectedly increased incidences of both stroke and dementia. The disparities between basic research studies that demonstrate neuroprotective effects of estrogen and progesterone and recent clinical findings that report adverse neural effects of hormone therapy indicate the need for a more complete understanding of estrogens and progesterone interactions in brain and other tissues. One important issue that is not well understood is how neural effects of estrogens are affected by progestagens. Recent experimental evidence shows that prolonged progesterone exposure often represses estradiol function. The mechanism by which progesterone inhibits estrogen action in the brain is unclear. We hypothesize that progesterone might oppose estrogen activity by regulating the expression and or function of estrogen receptors, ERα and ERβ, thereby affecting ER-dependent transcriptional activity and E2-mediated neuroprotection. My thesis work involved testing these hypotheses and in the following chapters, I provide the experimental evidence for the same. Chapter 1 is a comprehensive introduction to a number of topics that are relevant to my research area. Chapter 2 describes the effects of progesterone on the expression of estrogen receptors both in primary neuron cultures as well as in rat brains.; Chapter 3 describes the effect of progesterone regulation of estrogen receptors on estrogen-mediated transcriptional activity and neuroprotection against apoptotic factors primarily in cell-culture and to some extent in organotypic cultures. Chapter 4 describes the effects of estradiol and progesterone individually as well as combined on the expression of β-amyloid degrading enzymes and the accumulation of amyloid both in vitro and in vivo. In Chapter 5 we look at the effects of progesterone on apoptotic pathways by itself and in the presence of estradiol mainly in primary neurons. In Chapter 6 I discuss the relevance of my research findings in the context of neurobiology and translational research and predict the potential outcomes of incorporating these findings in hormone therapy against risk for neurodegenerative diseases such as Alzheimer’s disease. |
| Keyword | estrogen; progesterone; Alzheimer's disease; neuron |
| 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-m3298 |
| Rights | Jayaraman, Anusha |
| 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-Jayaraman-3898 |
| Archival file | uscthesesreloadpub_Volume35/etd-Jayaraman-3898.pdf |
Description
| Title | Page 1 |
| Full text | ESTROGEN AND PROGESTERONE INTERACTIONS IN NEURONS: IMPLICATIONS FOR ALZHEIMER’S DISEASE-RELATED PATHWAYS By Anusha Jayaraman 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) August 2010 Copyright 2010 Anusha Jayaraman |
Comments
Post a Comment for Page 1
