Medical Sciences Commons^™

Beyond The Brain: A Study Of Α-Synuclein's Role In Bone And Adipose Tissue, Carolina A. Figueroa

Electronic Theses and Dissertations

α-Synuclein is a polypeptide encoded by the Snca gene, highly expressed in neurons, but it is also found in bones and adipose tissue. Co-expression analysis showed that Snca regulates skeletal homeostasis, and its deletion reduced estrogen deficiency-induced bone loss and weight gain. It is a major component of Lewy bodies (LB) in Parkinson’s disease (PD), leading to progressive immobilization and a range of nonmotor symptoms, including osteopenia, body composition alterations and insulin resistance. This thesis aimed to determine α-Synuclein’s intrinsic role in bone and adipose homeostasis. We discussed the PD pathophysiology emphasizing aspects of bone health and metabolism. By using …

Therapeutic Potential Of A Ketogenic Diet In The Treatment Of Major Depressive Disorder, Jordan A. Murrin

Masters Theses, 2020-current

Major depressive disorder (MDD) is the second most common mental health condition and a leading cause of disability in the world. It is theorized that MDD develops from a combination of biological, psychological, and social stressors. The condition is typically treated using pharmaceuticals and psychotherapy. However, not all individuals with MDD have access to or choose to use these treatments, or may prefer to incorporate therapeutic lifestyle changes such as exercise, sleep, and healthy eating. Even with treatment, MDD can alter brain structure and function, leading to the development of comorbid mental health and chronic metabolic conditions like obesity, cardiovascular …

Tumor-Derived Exosomes Drive Immunosuppressive Macrophages In A Pre-Metastatic Niche Through Nf-Kβ Dependent Glycolytic Metabolic Reprogramming., Samantha M. Morrissey

Electronic Theses and Dissertations

The formation of a pre-metastatic niche is a fundamental requirement for primary tumor metastasis. One of the defining characteristics of a pre-metastatic niche is infiltration of immunosuppressive macrophages. However, how these macrophages acquire their immunosuppressive phenotype remains largely unexplored. Here, we demonstrate that tumor-derived exosomes (TDE) polarize macrophages towards an immunosuppressive phenotype characterized by increased PD-L1 expression through NF-kB-dependent metabolic reprogramming in mice and humans. While NF-κB has previously been shown to act as a direct transcription factor for PD-L1, we report a novel mechanism where TDE-induced NF-κB activation drives PD-L1 expression by augmenting the glycolytic capacity of macrophages through …

Microrna-148a Regulates Low-Density Lipoprotein Metabolism By Repressing The (Pro)Renin Receptor, Na Wang, Lishu He, Hui Lin, Lunbo Tan, Yuan Sun, Xiaoying Zhang, A. H. Jan Danser, Hong S. Lu, Yongcheng He, Xifeng Lu

Saha Cardiovascular Research Center Faculty Publications

High plasma LDL cholesterol (LDL-c) concentration is a major risk factor for atherosclerosis. Hepatic LDL receptor (LDLR) regulates LDL metabolism, and thereby plasma LDL-c concentration. Recently, we have identified the (pro)renin receptor [(P)RR] as a novel regulator of LDL metabolism, which regulates LDLR degradation and hence its protein abundance and activity. In silico analysis suggests that the (P)RR is a target of miR-148a. In this study we determined whether miR-148a could regulate LDL metabolism by regulating (P)RR expression in HepG2 and Huh7 cells. We found that miR-148a suppressed (P)RR expression by binding to the 3’-untranslated regions (3’-UTR) of the (P)RR …

Metabolic Requirements Of Nk Cell Responses To Viral Infection, Annelise Yoo Mah-Som

Arts & Sciences Electronic Theses and Dissertations

In recent years, the field of immunometabolism – the study of how specific changes in cellular metabolism regulate the function of diverse immune cell types—has grown exponentially. Several in vitro studies have examined the metabolic regulation of natural killer (NK) cells, which are first responders for viral infection and malignant transformation; however, much less is known regarding the role of metabolism in directing NK cell responses in vivo, such as during viral infection. In order to examine how NK cell antiviral function is regulated in vivo, we used a wellcharacterized infection with murine cytomegalovirus (MCMV) to assess NK cell cytokine …

Visualizing Metabolic Network Dynamics Through Time-Series Metabolomic Data., Lea F Buchweitz, James T Yurkovich, Christoph Blessing, Veronika Kohler, Fabian Schwarzkopf, Zachary A King, Laurence Yang, Freyr Jóhannsson, Ólafur E Sigurjónsson, Óttar Rolfsson, Julian Heinrich, Andreas Dräger

Articles, Abstracts, and Reports

BACKGROUND: New technologies have given rise to an abundance of -omics data, particularly metabolomic data. The scale of these data introduces new challenges for the interpretation and extraction of knowledge, requiring the development of innovative computational visualization methodologies. Here, we present GEM-Vis, an original method for the visualization of time-course metabolomic data within the context of metabolic network maps. We demonstrate the utility of the GEM-Vis method by examining previously published data for two cellular systems-the human platelet and erythrocyte under cold storage for use in transfusion medicine.

RESULTS: The results comprise two animated videos that allow for new insights …

Acute Blockade Of Pacap-Dependent Activity In The Ventromedial Nucleus Of The Hypothalamus Disrupts Leptin-Induced Behavioral And Molecular Changes In Rats, Matthew M. Hurley, Eden M. Anderson, Christopher Chen, Brian Maunze, Evan Michael Hess, Megan E. Block, Neerali Patel, Zane Cooper, Riley Mccoy, Tanya Dabra, William Conley, Michael J. Reilly, Matthew C. Hearing, Sujean Choi

Biomedical Sciences Faculty Research and Publications

Leptin signaling pathways, stemming primarily from the hypothalamus, are necessary for maintaining normal energy homeostasis and body weight. In both rodents and humans, dysregulation of leptin signaling leads to morbid obesity and diabetes. Since leptin resistance is considered a primary factor underlying obesity, understanding the regulation of leptin signaling could lead to therapeutic tools and provide insights into the causality of obesity. While leptin actions in some hypothalamic regions such as the arcuate nuclei have been characterized, less is known about leptin activity in the hypothalamic ventromedial nuclei (VMN). Recently, pituitary adenylate cyclase activating-polypeptide (PACAP) has been shown to reduce …

Apoe As A Metabolic Regulator In Humans, Mice, And Astrocytes, Brandon C. Farmer

Theses and Dissertations--Physiology

Altered metabolic pathways appear to play central roles in the pathophysiology of late-onset Alzheimer’s disease (AD). Carrier status of the E4 allele of the APOE gene is the strongest genetic risk factor for late-onset AD, and increasing evidence suggests that E4 carriers may be at an increased risk for neurodegeneration based on inherent metabolic impairments. A new appreciation is forming for the role of APOE in cerebral metabolism, and how nutritional factors may impact this role. In chapter 1, the literature on nutritional interventions in E4 carriers aimed at mitigating disease risk is reviewed. Studies investigating the mechanism by which …

Investigations Of A Low Carbohydrate Ketogenic Diet As A Possible Treatment For Malignant Brain Tumors, Elizabeth Anaya

Regis University Student Publications (comprehensive collection)

Cancer is now the leading cause of premature death in the U.S. and second worldwide. However, all cancers on average have seen a 20% increase in 5-year survival in the last 30 years. This is not true for brain cancers which have only seen a 1% increase. Brain cancer is extremely hard to treat, costing the most money out of any other cancer. Nevertheless, Otto Warburg’s investigation of cancer as a metabolic disease has led to a variety of new promising treatments. One of these treatments involves starving cancer cells by cutting off their access to glucose, a key component …

Understanding And Targeting Glucose Transporter 3 In Glioblastoma, Catherine Jeanne Libby

All ETDs from UAB

Glioblastoma (GBM) is the most common adult primary malignant brain tumor with a median survival of about 15 months, even after aggressive treatment. Treatment of GBM is difficult for multiple reasons including the location of the tumor, tumor invasiveness, and the high degree of both inter-and intra-tumoral heterogeneity. Contributing to intratumoral heterogeneity are highly tumorigenic, stem-like tumor cells, with the capacity to self-renew and propagate the tumor, termed brain tumor initiating cells (BTICs). BTICs are also commonly therapy resistant, highly invasive, and metabolically plastic with elevated expression of glucose transporter 3 (GLUT3) allowing them to preferentially survive in low nutrient …