archives@tulane.edu / The broad goal of the following experiments was to determine the mechanisms through which estrogen receptor (ER) α can maintain memory and enhance hippocampal function in the absence of endogenous or exogenously administered ovarian hormones. In Aim 1, we compared the subcellular localization of ERα and the expression of memory-related genes and proteins in the hippocampus following either continuous or previous exposure to estradiol in aging ovariectomized rats. Previous estradiol exposure, like continuous estradiol treatment, immediately following ovariectomy specifically increased the nuclear pool of ERα and resulted in lasting increases in gene transcription and protein expression in the hippocampus. In Aim 2, we demonstrated that insulin-like growth factor-1 (IGF-1) and brain-derived neuroestrogens interact to facilitate activation of hippocampal ERα and enhancement of memory in recently ovariectomized rats. Specifically, we showed that acute infusions of IGF-1 to the brains of ovariectomized middle-aged rats resulted in increased phosphorylation of hippocampal ERα, increased activation of the MAPK signaling pathway, and enhanced performance on the radialarm maze task, but that these effects were dependent on concurrent neuroestrogen synthesis. In Aim 3, we investigated the impacts of long-term ovarian hormone deprivation and previous estradiol treatment on the ability of IGF-1 and neuroestrogen signaling to maintain hippocampal function and memory. Results demonstrated that following long periods of ovarian hormone deprivation, neuroestrogens no longer contribute to ER-dependent transcriptional activity in the brain, a change which coincides with decreased interactions between IGF-1 and neuroestrogen signaling in the hippocampus and the subsequent effects on memory. However, previous exposure to estradiol during midlife maintains the interactions between IGF-1 and neuroestrogen signaling long after termination of estradiol treatment, resulting in long-lasting enhancements in memory and hippocampal function. Together, these experiments demonstrate a complex mechanism through which IGF-1, neuroestrogens, and ERα interact to maintain hippocampal dependent memory in the absence of circulating estrogens. / 1 / Nina E Baumgartner
| Identifer | oai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_121969 |
| Date | January 2021 |
| Contributors | Baumgartner, Nina (author), Daniel, Jill (Thesis advisor), School of Science & Engineering School of Science and Engineering (Degree granting institution), NULL (Degree granting institution) |
| Publisher | Tulane University |
| Source Sets | Tulane University |
| Language | English |
| Detected Language | English |
| Type | Text |
| Format | electronic, pages: 129 |
| Rights | No embargo, Copyright is in accordance with U.S. Copyright law. |
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