Estrogen regulation of neurotrophin systems in basal forebrain circuits : a dissertation /
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| Format: | Thesis Book |
| Language: | English |
| Published: |
[College Station, Tex.] :
[Texas A&M University],
[2000]
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| Subjects: |
| Abstract: | ABSTRACT: Estrogen receptors are colocalized with neurotrophin peptides and receptors in forebrain regions where neurotrophins have been shown to promote neuronal survival. Previous work indicates that estrogen increases mRNA expression of neurotrophins and their ligand-specific tyrosine kinase receptors (trks), while decreasing transcription of p75, the universal neurotrophin receptor. These studies test the hypothesis that estrogen regulates neurotrophin protein expression, transport and signal transduction in the forebrain of young adult and reproductively senescent rats. The data indicate that hormonal regulation of growth factor systems in estrogen-sensitive areas in region-, peptide-, and age-specific and results in estrogen-dependent functional modifications of forebrain circuits. In the prototypic septobulbar circuit, extending from the basal forebrain to the olfactory bulb, estrogen increases BDNF protein availability, as well as the expression of its cognate receptor, trkB. Further, estrogen enhances trkB-dependent retrograde translocation of exogenous BDNF in this circuit and increases afferent-signaling. By increasing trk protein and concomitantly decreasing p75, estrogen alters the trk/p75 ration in the olfactory bulb. Consequently, neurotrophin-stimulated MAP kinase activation is modified, resulting in the activation of pro-survival pathways in estrogen-treated animals. Collectively, these data suggest that estrogen-dependent enhancement of trk synthesis may increase neurotrophin trafficking and signaling in basal forebrain circuits, which are critically dependent on target-derived growth factors. Recent studies suggest that estrogen replacement therapy may decrease the risk for neurodegenerative diseases. In view of evidence suggesting that decreased trophic factor availability may contribute to the etiology of these diseases, the current studies elucidate a possible mechanism of estrogen's neuroprotective actions. |
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| Item Description: | Vita. "Major Subject: Medical Sciences". "Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment for the requirements for the degree of Doctor of Philosophy December 2000." Approved as to style and content by: Farida Sohrabji, Rajesh C. Miranda, William Griffith, Mark Zoran, James R. West. |
| Physical Description: | xii, 135 leaves : illustrations (some color) ; 28 cm. |
| Bibliography: | Includes bibliographical references (leaves 111-134). |