Effects of glyceollin on mRNA expression in the female mouse brain.

Glyceollin;brain;microarray;rna-seq;qPCR;phytoalexin

Sanaya Firdaus Bamji

University:University of Louisville

Department:Biology

关键词: Glyceollin;    brain;    microarray;    rna-seq;    qPCR;    phytoalexin;   

Others  :  https://ir.library.louisville.edu/cgi/viewcontent.cgi?article=3608&context=etd

美国|英语

来源: The Universite of Louisville's Institutional Repository

【 摘 要 】

Glyceollins (Glys), produced by soy plants in response to stress, have anti-estrogenic activity in breast and ovarian cancer cell lines in vitro and in vivo. In addition to known anti-estrogenic effects, Glys exhibit mechanisms of action not involving estrogen receptor (ER) signaling. To date, effects of Glys on brain physiology and function are unknown. The purpose of the experiments summarized in this dissertation was to gain an understanding of the effects of Gly on brain-related functions in the female mouse brain through the observation of changes in gene expression. For our initial studies, we treated ovariectomized Swiss Webster (CFW) mice with 17-β estradiol (E2) or placebo pellets, followed by 11 days of exposure to Glys or vehicle i.p. injections. We then performed microarray (Chapter 2) and RNA-sequencing analyses (Chapter 3) on total RNA extracted from whole brain hemispheres and identified differentially expressed genes (DEGs) between our treatment groups. Our results suggested that Glys, when in combination with E2 (E2+Gly), can oppose the E2 effects on gene expression and vice versa, can regulate genes similarly to E2, and can also have E2-independent effects on gene expression in the female brain. However, the whole brain experiments did not take into account the heterogeneity of the brain. Different brain regions perform unique and distinct functions and can differ markedly in terms of gene expression, so we wanted to determine if Glys had any brain region-specific effects on gene expression. Additionally, as the whole brain studies only included a single time point of exposure to Glys, we evaluated the effects of a single acute dose of Glys (2, 24 and 48 hr) as well as chronic exposure to Glys (multiple doses of Glys for 7 consecutive days) on gene expression in distinct brain regions. Therefore, in Chapter 4, we evaluated the effects of acute vs. chronic doses of Glys alone and in combination with E2 on gene expression in the hypothalamus, hippocampus, and cortex of the female mouse brain. Our results suggest that Glys can rapidly upregulate the expression of genes like growth hormone (Gh) in the hypothalamus, hippocampus and cortex and prolactin (Prl) in the hypothalamus and cortex, 2h or 24h after administration of a single acute dose. Thus Glys may potentially affect neuronal processes like food intake, stress and cognition through its effects on Gh and Prl gene expression in the female mouse brain. As all of the above chapters involve a