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All Subjects: Depression
All Subjects: Irritable Bowel Syndrome

Vitamin D-mediated Regulation of Anti-Aging Klotho and FOXO Signaling

Description

Vitamin D, Klotho, and FOXO3 have all been linked to have anti-aging and anti-cancerous effects as separate pathways. Specifically, mice with knockout Klotho in their genes have displayed signs of premature aging, humans who are vitamin D deficient have been shown to develop cardiovascular disease and cognitive impairments, and those who have displayed overexpression of FOXO3 have shown to have a longer lifespan. Here we took each pathway and attempted to formulate a feedback mechanism loop linking all three separate pathways. We propose that vitamin D levels modulate klotho activity, including the expression of the s-klotho and m-klotho isoforms. Moreover, the anti-oxidation transcription factor FOXO3 is also thought to participate in crosstalk with VDR signaling. Through the connection between 1,25D and Klotho, we probed at their interactions with FOXO3 signaling in kidney and colon cells, and proposed that vitamin D and klotho may reduce oxidative stress and suppress the onset of epithelial cancers through it effects on FOXO3. Results showed a strong support for the cooperation between FOXO3 and 1,25D to stimulate both superoxide dismutase (a FOXO3 response element) and XDR3/ROC (vitamin D response elements). This cooperation was mostly seen in embryonic kidney cells (HEK293) and not in the colon cancer cells (HCT116), which has led to the conclusion that vitamin D and FOXO3 cooperation mainly occurs in kidney tissue and/or in tissue that is not yet been overtaken by cancer. Differences in the Klotho isoforms were seen when measuring FOXO3 and vitamin D activity, but experiments manipulating other components will need to be conducted to further understand the function of Klotho in maintaining reactive oxygenated species levels.

ContributorsSandoval, Ruby (Author) / Jurutka, Peter (Thesis director) / Sandrin, Todd R. (Committee member) / Heck, Michael (Committee member) / School of Social and Behavioral Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)

Created2016-05

Identification of Differentially Expressed Genes as Biomarkers for Diagnosis of Irritable Bowel Syndrome (IBS): A Pilot Gene Discovery Hypothesis Generating Study

Description

The diagnosis of irritable bowel syndrome (IBS) is currently based on symptomatic criteria that exclude other conditions affecting the gastrointestinal tract, such as celiac disease, food allergies, and infections. The absence of appropriate diagnostic and therapeutic approaches for IBS places a significant burden on the patient and the health care system due to direct and indirect costs of care. Limitations associated with the application of symptomatic criteria include inappropriate use and/or intrinsic limitations such as the population to which these criteria are applied. The lack of biomarkers specific for IBS, non-specific abdominal symptoms, and considerable variability in the disease course creates additional uncertainty during diagnosis. This project involved screening tissue samples from patients with verified IBS to identify gene expression-based biomarkers associated with IBS. Through validation of microarray gene chip data on the tissue samples using PCR, it was determined that a number of genes within the diseased IBS patient tissue samples were differentially expressed in comparison to the healthy subjects. These findings could potentially lead to the diagnosis of IBS on the basis of a genetic "fingerprint".

ContributorsHockley, Maryam (Author) / Jurutka, Peter (Thesis director) / Sandrin, Todd (Committee member) / Zhang, Lin (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)

Created2013-12

The Importance of Studying Interactions With Ovarian Hormones: Implications for Depressive Symptoms in Premenopausal and Menopausal Women

Description

The relevance of depression in the clinical realm is well known, as it is one of the most common mental disorders in the United States. Clinical depression is the leading cause of disease for women worldwide. The sex difference in depression and anxiety has guided the research of not just recent studies but older studies as well, supporting the theory that gonadal hormones are associated with the mechanisms of emotional cognition. The scientific literature points towards a clear correlative relationship between gonadal hormones, especially estrogens, and emotion regulation. This thesis investigates the neural pathways that have been indicated to regulate mood and anxiety. Currently, the research points to the hypothalamic-pituitary-adrenal axis, which regulates the stress response through its ultimate secretion of cortisol through the adrenal cortex, and its modulated response when exposed to higher levels of estrogen. Another mechanism that has been investigated is the interaction of estrogen and the serotonergic system, which is noteworthy because the serotonergic system is known for its importance in mood regulation. However, it is important to note that the research seeking to determine the neurobiological underpinnings of estrogen and the serotonergic system is not expansive. Future research should focus on determining the direct relationship between cortisol hypersecretion and estrogens, the specific neurobiological effects of serotonergic receptor subtypes on the antidepressant actions of estrogens, and the simultaneous effects of the stress and serotonergic systems on depressive symptoms.

ContributorsArroyo, Mariana (Author) / Bimonte-Nelson, Heather (Thesis director) / Jurutka, Peter (Committee member) / School of International Letters and Cultures (Contributor) / School of Social and Behavioral Sciences (Contributor) / Barrett, The Honors College (Contributor)

Created2021-05