Ovarian aging of astrocytes : implications for neuronal repair and survival : a dissertation /
| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
College Station, Tex. :
Texas A&M University System Health Science Center,
2008.
|
| Subjects: |
| Abstract: | ABSTRACT: A critical physiological event for women is the menopause, which results in the loss of ovarian hormones such as estrogen. This reproductive senescence or ovarian aging increases a woman's risk for developing neurodegenerative diseases such as Alzheimer's disease. Further, using an animal model of menopause, our laboratory has shown that estrogen-replacement in "menopausal" rats is detrimental to several physiological processes as compared to young cycling females. The proposed studies examined the impact of ovarian aging on an important brain support cell, the astrocyte. Specifically, these studies determined the effects of exogenous estrogen and ovarian age on the ability of astrocytes to modulate the inflammatory response and promote neuronal repair. The genomic actions of estrogen are mediated through two receptors, estrogen receptor alpha (ER[alpha]) and beta (ER[beta]). When young adult- and senescent-derived astrocytes were pre-treated with compounds that had a selective binding affinity for one or both of the receptors, the inflammatory response was significantly attenuated following treatment with an endotoxin, suggesting that astrocytes from both ages of females were equally responsive to estrogen. However, when young adult-derived microglia were treated with these same compounds, only the ER[beta]-specific compound attenuated the inflammatory response. Thes studies suggest that compounds that act on ER[beta] may be more efficacious in modulating the inflammatory response as they act on both astrocytes and microglia. The next studies examined how ovarian aging affected the ability of astrocytes to promote neuronal differentiation. In senescent astrocytes the extracellular matrix, cytoskeletal features, and trophic factor expression were dramatically different from young adult astrocytes. Further, senescent astrocytes were unable to promote neuronal differentiation when co-cultured with neural progenitor cells to the same extent as young adult astrocytes, and, estrogen treatment was only beneficial to young adult co-cultures. Thus phenotypic changes in senescent astrocytes were associated with reduced neuronal differentiation capabilities and estrogen was ineffective in overcoming these impairments. Collectively, These studies suggest that astrocytes from young and ovarian-aged females can effectively mount an inflammatory response and are equally estrogen-responsive. However, senescent astrocytes are less able to promote neuronal differentiation, suggesting that the ovarian-aged brain may be more susceptible to repair following injury. |
|---|---|
| Item Description: | Vita. "Major Subject: Medical Sciences". "Submitted to the Office of Research and Graduate Studies of The Texas A&M University System Health Science Center in partial fulfillment for the requirements for the degree of Doctor of Philosophy May 2008." Approved as to style and content by: Farida Sohrabji, Rajesh C. Miranda, William H. Griffith, Mark J. Zoran, William H. Griffith. |
| Physical Description: | x, 173 leaves : illustrations ; 28 cm. |
| Bibliography: | Includes bibliographical references (leaves 162-172). |