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-BASED HORMONE
THERAPY AND THE DEVELOPMENT OF ALZHEIMER’S DISEASE
by
Jenna C. Carroll
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(NEUROSCIENCE)
August 2009
Copyright 2009 Jenna C. Carroll
Object Description
| Title | Estrogen and progesterone-based hormone therapy and the development of Alzheimer's disease |
| Author | Carroll, Jenna C. |
| Author email | jccarrol@usc.edu; jennacarroll@hotmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Neuroscience |
| School | College of Letters, Arts and Sciences |
| Date defended/completed | 2009-05-07 |
| Date submitted | 2009 |
| Restricted until | Unrestricted |
| Date published | 2009-08-08 |
| Advisor (committee chair) | Pike, Christian, J |
| Advisor (committee member) |
Finch, Caleb Thompson, Richard Miller, Carol Mack, Wendy |
| Abstract | This dissertation seeks to investigate the broad issue of the effects of sex steroid hormones on neuroprotective measures related to aging and the prevention of the progression of Alzheimer’s disease (AD). In particular, this dissertation will focus on the effects of female sex steroid hormones, estrogen and progesterone both alone and in combination on AD in women. Abundant evidence implicates sex steroid depletion in postmenopausal women as a risk factor for the development of AD. However, there appears to be a disconnect between experimental data clearly establishing multiple estrogen protective functions, and clinical findings showing that estrogen-based hormone therapy fails to prevent and slow progression of cognitive decline and AD. Furthermore, while estrogen’s many beneficial effects in the brain have been well established, the effects of progesterone, both alone and in combination with estrogen, are currently unclear and under-investigated. The Women’s Health Initiative Memory Study (WHIMS) raised several questions regarding the actions of progestins in the brain and the efficacy of hormone therapy in lowering the risk of AD in post-menopausal women. These questions are the basis behind the experiments described in this dissertation; a) the effects of estrogen and progesterone, both alone and in combination on AD-like neuropathology, b) the difference between various, clinically-relevant progestin exposures in combination with estrogen, c) the “critical window hypothesis” of aging brain responsiveness, d) the effects of clinically-relevant selective estrogen receptor modulators (SERMs) and e) the effects of activational vs. organizational sex steroid hormone exposure.; The data demonstrate that aged rodents have altered neuroprotective responsiveness to the hormone treatment, that continuous progesterone treatment attenuates estrogen neuroprotection against kainate lesion and Aβ accumulation, cyclic progesterone has more beneficial effects than continuous progesterone treatment, synthetic estrogen-like compounds can mimic estrogen action, and that gender differences in AD pathogenesis can be regulated by perinatal hormone action. Overall, these results demonstrate that estrogen and progesterone therapies remain important and potentially powerful preventive and intervention strategies against AD and other age-related neurodegenerative disorders. Understanding the effects of both estrogen and progesterone in the brain is essential for future optimization of estrogen-based hormone therapy for the potential prevention and treatment of AD in post-menopausal women. |
| Keyword | estrogen; progesterone; Alzheimer's disease; beta amyloid; tau; transgenic |
| 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-m2547 |
| Rights | Carroll, Jenna 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-Carroll-2964 |
| Archival file | uscthesesreloadpub_Volume56/etd-Carroll-2964.pdf |
Description
| Title | Page 1 |
| Full text | ESTROGEN AND PROGESTERONE-BASED HORMONE THERAPY AND THE DEVELOPMENT OF ALZHEIMER’S DISEASE by Jenna C. Carroll A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (NEUROSCIENCE) August 2009 Copyright 2009 Jenna C. Carroll |
Comments
Post a Comment for Page 1
