Metabolomics Analysis of Brain Monoamines, Metabolites and Amino Acids in Two Models of Menopause with/without Estrogen Receptor Agonist TreatmentsLong, Tao (2019) Metabolomics Analysis of Brain Monoamines, Metabolites and Amino Acids in Two Models of Menopause with/without Estrogen Receptor Agonist Treatments. Doctoral Dissertation, University of Pittsburgh. (Unpublished)
AbstractEstrogens have many beneficial effects in the brain. Previous studies have evaluated effects of estrogens on specific neurotransmitter systems including dopaminergic, serotoninergic, noradrenergic as well as glutamatergic pathways. However, a comprehensive profile of the collection of neurochemical changes that occur following menopause and estrogen treatments within specific regions of the brain has not been available. Therefore, it is necessary to directly and systematically compare the effect of estrogens on these multiple interacting brain neurotransmitter (NT) pathways between the two clinically relevant menopauses: surgical menopause (OVX) and transitional menopause (VCD). In the first part of my thesis research, I comprehensively characterized and compared the neurochemical changes associated with surgical and transitional menopausal rat models in three regions of the brain at two time points. Naturally cycling rats sacrificed on proestrus (high estrogen level) and diestrus (low estrogen level) phases were also added to the investigation. Results showed that while many of the effects of surgical vs. transitional menopause were the same, there also were some important differences that varied by brain region and by time following the menopause. In the second part of this thesis, I further investigated and compared the effects of chronic treatments of estradiol (E2) and selective estrogen receptor (ER) agonists (PPT, DPN, G-1) on brain NT pathways between surgical and transitional menopause at two time points. The results demonstrated significant differences in the effects of ER agonist treatments on neurochemical endpoints in OVX vs. VCD-treated rats and the effects were also brain region-specific and time-dependent. These results were the first to systematically and simultaneously evaluate the effects of ER agonist treatments on multiple neurochemical endpoints in multiple regions of the brain in two models of menopause. The fact that agonist treatments had lesser effects in VCD-treated rats than in OVX rats may help to explain reports of lesser effects of estrogen replacement on cognitive performance in women that have undergone transitional vs. surgical menopause. Share
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