Does reproductive age modulate estrogen's effect on the inflammatory response? : a dissertation /
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| Format: | Thesis Book |
| Language: | English |
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College Station, Tex. :
Texas A&M University System Health Science Center,
2006.
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| Subjects: |
| Abstract: | ABSTRACTS: Estrogen replacement prior to brain injury has been reported to be neuroprotective. Previous studies have shown that estrogen reduces inflammation after injury in the young adult forebrain, whereas in a reproductive senescence model, inflammation is exacerbated by estrogen. Reproductive senescent females are older acyclic and physiologically resemble the human menopause. Since this is the group that is likely to seek estrogen replacement, understanding the effects of estrogen on neural inflammation is important. The present studies monitor how reproductive age modulates the neural inflammatory response and examines the cellular locus of estrogen's dichotomous actions. The data indicates that microglia from young adult and aged hosts do not suppress LPS-induced IL-β expression when pretreated with 17β-estradiol. However, circulating immune cells from estrogen pretreated young adult females had a significant suppression of LPS-stimulated cytokine expression, whereas in senescent animals, expression was increased. This was similar to the pattern of estrogen action seen in the brain injury model and suggested that circulating immune cells rather than microglia are altered by reproductive aging. Since the brain typically excludes circulating immune cells via the blood brain barrier, it is possible that neural inflammation resulting from a systemic inflammatory event would differ from that caused by local injury. To test the role of the aging blood brain barrier, young and senescent animals were injection systemically with LPS, and central and peripheral cytokine expression was measured. In young adults, estrogen suppressed IL-1β expression the olfactory bulb (protected by the blood brain barrier) but not in the pituitary gland (only partially protected by the blood brain barrier). In senescent females, estrogen replacement completely suppressed IL-1β in the pituitary and olfactory bulb, as well as lowered plasma corticosteroids, indicating that hormone treatment delayed the initiation of the immune response. Collectively, these data confirm that the inflammatory response is altered by reproductive age and extend these analyses to show that estrogen's age dependent effects on neural inflammation may actually be due to age-related changes in circulating immune cells and/or the blood brain barrier. These studies support the idea that compensatory changes incurred during reproductive aging may be incompatible with estrogen replacement. |
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| Item Description: | Vita. "Major Subject: Medical Sciences". Approved as to style and content by: Farida Sohrabji, Rajesh Miranda, Wei-Jung Chen, Jane Welsh, John Gelderd. |
| Physical Description: | x, 135 leaves : illustrations ; 28 cm. |
| Bibliography: | Includes bibliographical references. |