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Articles 31 - 60 of 308
Full-Text Articles in Physiology
Investigation Of Molecular Mechanisms Of Liver Preservation Injury: A Complication Preceding Organ Transplantation, Ria C. Fyffe-Freil
Investigation Of Molecular Mechanisms Of Liver Preservation Injury: A Complication Preceding Organ Transplantation, Ria C. Fyffe-Freil
Theses and Dissertations
Of the over 108,000 American awaiting a life-saving organ transplant today, over 12,000 (11%) of those need a new liver (OPTN, 2020). Last year, only 35% of patients on the waiting list for an organ were transplanted. Improving the quality of marginal organs by preventing or reversing preservation injury could vastly increase the number of transplants performed. Washout of circulating blood during liver procurement with cold University of Wisconsin solution flushes out any endogenous pro-survival signaling molecules. We investigated lysophospholipid (LPL) surface receptors (G-protein coupled receptors for lysophosphatidic acid (LPA) and sphingosine- 1-phosphate (S1P)) and their role in protecting hepatocytes …
Role Of Transient Receptor Potential Channels In Epithelial Morphogenesis In Chick Embryo, Trinity Q. Waddell
Role Of Transient Receptor Potential Channels In Epithelial Morphogenesis In Chick Embryo, Trinity Q. Waddell
Theses and Dissertations
Transient Receptor Potential channels (TRP) are a superfamily of cationic specific ionchannels that are regulated by various stimuli such as temperature, pH, mechanical stress, ligandsand ion concentration. The role of TRP channels in disease states such as autosomal dominantpolycystic kidney disease, cancer metastasis, and developmental defects lend credence to thebelief that they play an important part in epithelial morphogenesis events. The development ofsomites, neural tube closure and migration of neural crest cells to form things such as the faceand heart is a good developmental model for the aforementioned cellular processes. We haveshown that TRP channels can be found in the …
Incidental Cardiac Arrhythmia Identification With Consumer Grade Heart Rate Monitors: A Case Study, Neal C. Phifer
Incidental Cardiac Arrhythmia Identification With Consumer Grade Heart Rate Monitors: A Case Study, Neal C. Phifer
Theses and Dissertations
PURPOSE: The purpose of the study was to examine instances of using chest strap type heart rate monitor (HRM) data as a means of identifying otherwise asymptomatic individuals with possible cardiac arrhythmias as examined across four division one collegiate sports teams. METHODS: Heart rate activity was tracked across an entire season of four different division one collegiate teams (men’s basketball, women’s basketball, women’s soccer and women’s volleyball). A total of 65 athletes were equipped with heart rate monitors that were worn as allowed during practices and games. Data were collected using chest strap mounted activity sensors (Polar Team Pro sensors …
Deciphering The Consequences Of Yolk Testosterone Metabolism In Birds, Nicole A. Campbell
Deciphering The Consequences Of Yolk Testosterone Metabolism In Birds, Nicole A. Campbell
Theses and Dissertations
Maternal steroids transferred to eggs can elicit permanent effects on various aspects of offspring phenotype. Although, testosterone was thought to be a key mediator of maternal effects in birds, we now know that vertebrate embryos actively regulate their exposure to maternal testosterone through steroid metabolism, suggesting testosterone metabolites may elicit the observed phenotypic effects. To address the role steroid metabolism plays in mediating yolk testosterone effects, we used European starling (Sturnus vulgaris) eggs to characterize the timing of testosterone metabolism and determine whether etiocholanolone, a prominent testosterone metabolite in avian embryos, is capable of influencing early embryonic development. Tritiated testosterone …
Diuretic And Natriuretic Activity Of Faah Inhibition In The Renal Medulla: A Proposed Role Of Palmitoylethanolamide And Its Regulation By Renal Medullary Interstitial Cells, Sara Dempsey
Theses and Dissertations
Hypertension is a critical public health issue worldwide, and in the United States, it is the leading cause of heart disease, stroke, and kidney failure, contributing to more than 1,100 deaths per day. It is proposed that the renal medulla combats increased blood pressure by releasing a neutral lipid from the lipid droplets of medullary interstitial cells, termed medullipin, which induces diuresis- natriuresis and vasodepression. The renal medulla is enriched with fatty acid lipid ethanolamides including the endocannabinoid anandamide (AEA), palmitoylethanolamide (PEA), and oleoylethanolamide (OEA), along with their primary hydrolyzing enzyme fatty acid amide hydrolase (FAAH). Our lab is investigating …
An Evaluation Of Induced Shear Stress On Endothelial Cellular Adhesion Molecules, Edward B. Crabb
An Evaluation Of Induced Shear Stress On Endothelial Cellular Adhesion Molecules, Edward B. Crabb
Theses and Dissertations
The pathophysiology of atherosclerotic cardiovascular disease (CVD) is highlighted by vascular dysfunction and low-grade vascular inflammation. Furthermore, the site-specific distribution of atherosclerosis throughout the arterial vasculature is primarily determined by local hemodynamic force. Therefore, this dissertation outlines three experiments designed to investigate the role of acute mental and physical (i.e., aerobic exercise), and vascular wall shear stress (SS) on the inflammatory aspects of atherosclerosis. Chapter 2 examines the effect of acute laboratory-induced mental stress on intracellular pro-inflammatory signaling pathways in peripheral blood mononuclear cells. Chapter 3 investigates the impact of acute laboratory-induced mental stress and maximal aerobic exercise on the …
Embryonic Stem Cell-Derived Exosomes Increase The Antiproliferative Activity Of Doxorubicin In Breast Cancer, Alexander M. Hirsch
Embryonic Stem Cell-Derived Exosomes Increase The Antiproliferative Activity Of Doxorubicin In Breast Cancer, Alexander M. Hirsch
Theses and Dissertations
The field of cancer research has grown immensely in recent decades and has led to a better understanding of the causes of the disease, as well as greatly improved treatment for various types of cancers, especially breast cancer. One of the most effective treatments involves the chemotherapeutic drug doxorubicin (DOX). DOX is an effective tool against all types of breast cancer, especially against triple negative breast cancer. However, DOX causes adverse side effects that include damage to the heart and skeletal muscle, particularly above specific cumulative doses. Recent evidence suggests that embryonic stem cell-derived (ES) exosomes, nanoscale extracellular vesicles that …
Molecular Targets Of Psychedelics And Their Role In Behavioral Models Of Hallucinogenic Action, Hiba Z. Vohra
Molecular Targets Of Psychedelics And Their Role In Behavioral Models Of Hallucinogenic Action, Hiba Z. Vohra
Theses and Dissertations
Psychedelics are a subset of hallucinogenic drugs that exert their characteristic effects through agonist activity at the serotonin receptor 2A (5-HT2A). In this study, I aimed to characterize the modulatory role of the metabotropic glutamate subtype 2 receptor (mGluR2) in the 5-HT2A-specific rodent model of hallucinogenic action, head-twitch response (HTR). Secondly, I aimed to explore if 5-HT2A agonist-induced deficits in prepulse inhibition (PPI) of the startle response, an additional model of hallucinogenic action, could be produced in mice. Though 5-HT2A agonist-induced PPI deficits, which represent interruptions in normal sensorimotor gating, have been described in …
Electrostatic Networks And Mechanisms Of Δph-Dependent Gating In The Human Voltage-Gated Proton Channel Hv1, Ashley L. Bennett
Electrostatic Networks And Mechanisms Of Δph-Dependent Gating In The Human Voltage-Gated Proton Channel Hv1, Ashley L. Bennett
Theses and Dissertations
The structure of the voltage-gated proton (H+) channel Hv1 is homologous to the voltage sensor domain (VSD) of tetrameric voltage-gated Na+, K+ and Ca2+ channels (VGCs), but lacks a pore domain and instead forms a homodimer. Similar to other VSD proteins, Hv1 is gated by changes in membrane potential (V), but unlike VGCs, voltage-dependent gating in Hv1 is modulated by changes in the transmembrane pH gradient (DpH = pHo - pHi). In Hv1, pHo or pHi changes shift the open probability (POPEN)-V relation by ~40 mV per …
An Investigation On The Role Of Β-Arrestin 2, Protein Kinase C And Sex On The Mechanism Of Morphine Tolerance In The Mouse Ileum, Karan Hitesh Muchhala
An Investigation On The Role Of Β-Arrestin 2, Protein Kinase C And Sex On The Mechanism Of Morphine Tolerance In The Mouse Ileum, Karan Hitesh Muchhala
Theses and Dissertations
Opioids such as morphine are frequently used in the clinic to treat pain. However, the perennial bane of chronic opioid use is the rapid development of tolerance to the analgesic effects but delayed development of tolerance to the respiratory depressant and constipating effects. As constipation is one of the most common opioid-related adverse effects in humans, it is important to delineate mechanisms that drive opioid tolerance in the ileum and lack of it in the colon. The overarching goal of this thesis was to investigate mechanisms of morphine tolerance in the ileum by comparing the mechanism of morphine tolerance in …
Out Of The Shell: Exploring The Phagocytic Capabilities Of The B Cell And Isolated Lymphoid Follicle-Lie Structures In The Red-Eared Slider, Trachemys Scripta, Marc A. Ashford Jr.
Out Of The Shell: Exploring The Phagocytic Capabilities Of The B Cell And Isolated Lymphoid Follicle-Lie Structures In The Red-Eared Slider, Trachemys Scripta, Marc A. Ashford Jr.
Theses and Dissertations
Management of immunity is crucial for survival in all living organisms. While there is a large amount of research for established model organisms, such as the mouse model, much less is known about reptiles. When compared to immunity in mammals, we discover many differences such as susceptibility to certain pathogens, alteration of immune processes due to environmental temperature, the total absence of certain lymphoid organs contained in mammals, among many others. Despite this, the reptile has shown in many studies that they are worthy systems to study immunity in an evolutionary perspective and recent studies may show that they may …
Markers Of Cardiometabolic Risk And Thyroid Dysfunction In U.S. Adolescents: Nhanes Iii, Jonathan Austin
Markers Of Cardiometabolic Risk And Thyroid Dysfunction In U.S. Adolescents: Nhanes Iii, Jonathan Austin
Theses and Dissertations
The global prevalence of metabolic syndrome (MetS) and its associated components (high fasting glucose, waist circumference, blood pressure, triglycerides, and low HDL) have increased over the past few decades. In addition, abnormal thyroid hormone levels have been found to manifest in a cascade of metabolic dysfunction, which may be linked to MetS in youth. PURPOSE: The purpose of the study is to investigate the association between MetS, its components, and markers of thyroid function in a nationally-representative sample of adolescents. METHODS: The National Health and Nutrition Examination Survey III (1988-1994) collected data on the components of metabolic syndrome and thyroid …
Multi-Tissue Examination Of Exercise Or Metformin On The Consequences Of Doxorubicin Treatment, Amy Dee Mackay
Multi-Tissue Examination Of Exercise Or Metformin On The Consequences Of Doxorubicin Treatment, Amy Dee Mackay
Theses and Dissertations
Doxorubicin (DOX) is an effective chemotherapeutic treatment with lasting deleterious side effects in heart and skeletal muscle. As an increased percentage of patients live many years past their cancer treatments, addressing the long-term side effects of chemotherapy treatment becomes critical. In an attempt to prevent heart and skeletal muscle damage caused by DOX, two co-treatments, exercise (EX) or metformin (MET) were studied for their effectiveness in maintaining muscle function, mitochondrial respiration and iron regulation. DOX is known to bind with iron, contributing to oxidative damage resulting in cardiac and skeletal muscle toxicity. However, the degree to which the toxic side …
Crispr-Cas9 Transfection Optimization And Use In A Forward Genetic Screen To Identify Telomere Length Maintenance Genes, Kelsey Phillips
Crispr-Cas9 Transfection Optimization And Use In A Forward Genetic Screen To Identify Telomere Length Maintenance Genes, Kelsey Phillips
Theses and Dissertations
Mutations in the telomere length maintenance pathway can lead to a spectrum of diseases called telomere syndromes, however, the pathway is not fully understood and there may still be unknown components. We designed a forward genetic screen to identify new genes involved in telomere length maintenance. Of the top ranked genes, ZNF827, a zinc finger protein, is the most promising candidate gene. The possible discovery of a new component involved in telomere length maintenance increases our understanding of the pathway and opens new avenues of research. Recent advances in molecular biology techniques, such as the use of RNA-guided nuclease CRISPR …
Human Optimization And Performance Enhancement In Flight Via Real-Time Biofeedback (Project Have Hope), Michael S. Fritts
Human Optimization And Performance Enhancement In Flight Via Real-Time Biofeedback (Project Have Hope), Michael S. Fritts
Theses and Dissertations
A four-phase, chronological, and build-up approach was implemented that commenced with basic hardware testing in a centrifuge and culminated in flights augmented by real-time biofeedback displays. A prototype Portable Electrocardiogram Unit (PECGU) was designed and proven to accurately measure heart rate (HR) and display percent heart rate reserve (%HRR). Results showed that %HRR was not a sole predictor of cognitive state. Cognitive responses indicated some correlation with %HRR, but were influenced by environment (centrifuge vs. flight). Subjective perceived exertion levels did not show statistically significant changes during test with biofeedback. A G-tracking task was evaluated during centrifuge and flight tests. …
A Combinatorial Premotor Neural Code: Transformation Of Sensory Information Into Meaningful Rhythmic Motor Output By A Network Of Heterogeneous Modulatory Neurons, Christopher John Goldsmith
A Combinatorial Premotor Neural Code: Transformation Of Sensory Information Into Meaningful Rhythmic Motor Output By A Network Of Heterogeneous Modulatory Neurons, Christopher John Goldsmith
Theses and Dissertations
The goal of the following research was to investigate the contributions of neural networks in selecting distinct variants of rhythmic motor activity. We used the premotor commissural ganglion (CoG) in the stomatogastric nervous system of the Jonah crab to understand how this network effectively controls the rhythms produced in downstream motor circuits. Prior research determined that individual CoG neurons are necessary to mediate sensory-induced variation in the effected motor patterns. However, single premotor neuron inputs to the STG are not sufficient to recreate the patterns induced by the selective activation of sensory pathways. Thus, it was hypothesized that the CoG-mediated …
Regulation Of Hcn Channel Function By Direct Camp Binding And Singlet Oxygen, Vinaykumar Idikuda
Regulation Of Hcn Channel Function By Direct Camp Binding And Singlet Oxygen, Vinaykumar Idikuda
Theses and Dissertations
Hyperpolarization-activated, cyclic-nucleotide gated ion channels (HCN channels) are activated by membrane hyperpolarization and modulated by cyclic nucleotides. HCN channels are important to maintain the resting membrane potential and input resistance in neurons and have important physiological functions in the brain and heart. Four mammalian HCN isoforms, HCN1-4, and the isoform cloned from sea urchin, spHCN, have been extensively studied. Among these, only spHCN channel shows a voltage dependent inactivation. Previous studies have shown that the ligand binding in mHCN2 channel is activity dependent: cAMP binding increases along with channel opening or channels in the open state have higher binding affinity …
Utilizing Voltage-Gated Calcium Channels To Assess The Activity Of Cathinone Derivatives At Human Monoamine Transporters, Brian A. Ruiz
Utilizing Voltage-Gated Calcium Channels To Assess The Activity Of Cathinone Derivatives At Human Monoamine Transporters, Brian A. Ruiz
Theses and Dissertations
Cathinones are psychostimulant compounds heavily implicated as drugs of abuse. They exert their physiological actions at the monoamine transporters, which are responsible for maintaining synaptic neurotransmitter homeostasis. Monoamine transporters produce currents during transport and have been shown to depolarize cell membranes and activate voltage-gated calcium channels in mammalian expression systems. This phenomenon is harnessed in an assay which measures these induced calcium transients, allowing for quantification of pharmacodynamic effects of compounds at monoamine transporters. It is unknown if this electrical coupling occurs in neurons, but the implications if it does are significant. In the current work, fluorescent resonance energy transfer …
Branched Short Chain Fatty Acid Isovaleric Acid Causes Smooth Muscle Relaxation Via Camp/Pka Pathway, Inhibits Gastrointestinal Motility, And Disrupts Peristaltic Movement, Bryan Adam Blakeney
Branched Short Chain Fatty Acid Isovaleric Acid Causes Smooth Muscle Relaxation Via Camp/Pka Pathway, Inhibits Gastrointestinal Motility, And Disrupts Peristaltic Movement, Bryan Adam Blakeney
Theses and Dissertations
Isovaleric Acid (IVA) is a 5-carbon branched chain fatty acid present in fermented foods and produced by the fermentation of leucine by colonic bacteria. IVA activates G-protein coupled receptors such as FFAR2, FFAR3, and OR51E1 known to be expressed on enteric neurons and enteroendocrine cells. We previously reported that the shorter, straight chain fatty acids acetate, propionate and butyrate, differentially affect colonic propulsion; however, the effect of branched chain fatty acids on gastrointestinal motility is unknown. We hypothesize that IVA relaxes smooth muscle in a cAMP/PKA dependent manner by direct action on smooth muscle cells. IVA will also decrease peristalsis …
Role Of C121a In Mglur2 Homodimeric Expression And Function, Jong M. Shin
Role Of C121a In Mglur2 Homodimeric Expression And Function, Jong M. Shin
Theses and Dissertations
The group II metabotropic glutamate receptors are known for their involvement in various psychiatric disorders. The mGluR2 in particular is linked with etiology of schizophrenia especially in the context of crosstalk with 5-HT2A. Thus, the mGluR2 has attracted attentions for its potential therapeutic applications. Despite numerous physiological evidences on the actions of mGluR2, its mechanism is still unclear to this day. It is partially due to the lack of understanding in characteristics of mGluR2 homodimer which is its functionally active form. Therefore, the characterization of dimeric interaction serves as a foundation to advanced understanding of the role of mGluR2. On …
Impact Of Aerobic Exercise On Monocyte Subset Receptor Expression And Macrophage Polarization, Anson M. Blanks
Impact Of Aerobic Exercise On Monocyte Subset Receptor Expression And Macrophage Polarization, Anson M. Blanks
Theses and Dissertations
Atherosclerotic cardiovascular disease (CVD) is hallmarked by inflammatory immune activation, particularly by the induction of a response by monocytes. Classical (CD14++CD16-) are anti-inflammatory mediators under homeostatic conditions, while intermediate (CD14++CD16+) and non-classical (CD14LowCD16++) monocytes promote inflammation following activation. Monocyte activation and functionality is dependent upon receptor expression and ligand production by a variety of cells, including monocytes. Alterations in the expression of surface receptors often have a direct impact upon monocyte function, such as the increased pro-inflammatory cytokine production in response to activation that accompanies elevated CD14 expression …
Nicotinic Acetylcholine Receptor Dependent Effects Of Nicotine On Hek293t And Hbo Cells, James D. Larsen
Nicotinic Acetylcholine Receptor Dependent Effects Of Nicotine On Hek293t And Hbo Cells, James D. Larsen
Theses and Dissertations
T2R receptors are the classical bitter taste receptors which detect and transduce bitter taste in a subset of taste receptor cells (TRCs). The TRPM5-dependent T2Rs are G-protein coupled receptors (GPCRs) and are linked to G protein, gustducin to initiate an intracellular signaling cascade for the transduction of bitter tastants. Nicotine is bitter. However, at present the transduction mechanisms for the detection of nicotine in are poorly understood. Previous studies from our laboratory using TRPM5 knockout (KO) mice demonstrated that the T2R pathway is insufficient in explaining the taste perception of nicotine. TRPM5 KO mice elicited chorda tympani (CT) taste nerve …
Chronic Clozapine Treatment Impairs Functional Activation Of Metabotropic Glutamate Receptor 2 Via An Hdac2-Depedent Mechanism, Travis M. Cuddy
Chronic Clozapine Treatment Impairs Functional Activation Of Metabotropic Glutamate Receptor 2 Via An Hdac2-Depedent Mechanism, Travis M. Cuddy
Theses and Dissertations
Schizophrenia is a chronic mental disorder affecting millions worldwide. It has no known cure. Current pharmaceutical treatments have shown efficacy in only one of the three symptom clusters of schizophrenia, providing little or no benefit in the other two. Furthermore, the current standard-of-care drugs, known as atypical antipsychotics, carry risks of severe side effects affecting multiple body systems. Most patients opt to discontinue drug therapy within two years of initiation due to lack of efficacy and/or preponderance of adverse effects. Previous findings have shown that chronic usage of atypical antipsychotics causes a 5-HT2A-dependent upregulation of histone deacetylase 2 …
Temperature Effects On An Axon’S Ability To Maintain Phasing Of A Rhythmic Motor System, Marissa Elaine Cruz
Temperature Effects On An Axon’S Ability To Maintain Phasing Of A Rhythmic Motor System, Marissa Elaine Cruz
Theses and Dissertations
The precise timing of action potentials generated in the nervous system is crucial for generating adequate behavior. Once generated, action potentials travel along axons towards the neurons or muscles they innervate. Axons are also responsible for preserving the temporal fidelity of the generated action potentials. One challenge axons face is that they can be of considerable length, and exposed to changes in internal and external conditions. Temperature fluctuations, for example, affect the ion channels that generate and propagate action potentials causing changes in action potential speed. It is unclear if, and how, the timing of action potentials can be preserved …
Pharmaceutical And Natural (Exercise) Mechanisms To Mitigate The Negative Impact Of Ptsd And Chronic Stress On Synaptic Plasticity And Memory, Roxanne M. Miller
Pharmaceutical And Natural (Exercise) Mechanisms To Mitigate The Negative Impact Of Ptsd And Chronic Stress On Synaptic Plasticity And Memory, Roxanne M. Miller
Theses and Dissertations
Synapses can be altered due to experiences in a process called synaptic plasticity, which causes memory formations. Synapses can be strengthened through methods known as long-term potentiation (LTP) or weakened through long-term depression (LTD). Stresses can cause changes by altering synapses through either LTP or LTD. Rats were used to study the effects of post-traumatic stress disorder (PTSD)-like symptoms and a prophylactic treatment using pharmaceuticals. The first model used was the single prolonged stress (SPS) with two weeks of chronic light, which was not as effective for causing changes in synaptic plasticity. The second model, seven days of social defeat …
Mri T2 Signal Changes Indicate Tau Pathophysiology In A Murine Alzheimer's Disease Model, Rajan Deep Adhikari
Mri T2 Signal Changes Indicate Tau Pathophysiology In A Murine Alzheimer's Disease Model, Rajan Deep Adhikari
Theses and Dissertations
Pathogenesis, diagnosis and treatment, the essential domains in medical practice, seem helpless to address Alzheimer's disease (AD). With a huge mortality rate, it is looming and threatening the socioeconomic barrier. Despite many different studies, the pathogenesis of AD remains inconclusive. However, growing numbers of studies suggest oxidative stress to contribute to the initiation and progression of AD. We propose an iron hypothesis: iron mediated oxidative damage by reactive oxygen species (ROS), which induces protective roles of amyloid beta and hyper-phosphorylated tau (HP-tau) to sequester iron and limit the disease. We propose to study such mechanism using transgenic mice models for …
Modulation Of Synaptic Plasticity: Endocannabinoids And Novel G-Protein Coupled Receptors Expression And Translational Effects In Interneurons, Katrina M. Hurst
Modulation Of Synaptic Plasticity: Endocannabinoids And Novel G-Protein Coupled Receptors Expression And Translational Effects In Interneurons, Katrina M. Hurst
Theses and Dissertations
Learning and memory are important processes that occur in the brain. The brain is comprised of neurons that make connections with each other known as synapses. Synaptic plasticity is widely believed to be the physiologic mechanism by which learning and memory occur. Synapses can either be strengthened through a process known as long-term potentiation (LTP) or weakened through long-term depression (LTD). The area of the brain that is most studied for its role in learning and memory is the hippocampus, which has been shown to be involved in memory consolidation. The detection of endocannabinoids and their receptors has opened a …
The Mechanistic Requirements Of Passive H+ Import Through The Na, K-Atpase, Kevin S. Stanley
The Mechanistic Requirements Of Passive H+ Import Through The Na, K-Atpase, Kevin S. Stanley
Theses and Dissertations
This work focuses on the elucidation of the mechanism of passive proton import through the Na,K-ATPase. This enzyme uses the energy in ATP hydrolysis to exchange three intracellular Na+ for two extracellular K+ to maintain ion gradients within the cell, and while in the absence of physiological external Na+ and K+, the phosphorylated externally open (E2P) conformation passively imports protons, generating an inward current (IH). Chapter one reports on the effects of intracellular cations and nucleotides to shift the Na,K-ATPase into the E2P conformation. We identified that a combination of either internal Na+ and ATP or K+ and Pi. In …
Chemogenetic Stimulation Of Electrically Coupled Midbrain Gaba Neurons In Alcohol Reward And Dependence, Stephanie Suzette Pistorius
Chemogenetic Stimulation Of Electrically Coupled Midbrain Gaba Neurons In Alcohol Reward And Dependence, Stephanie Suzette Pistorius
Theses and Dissertations
The prevailing view is that enhancement of dopamine (DA) transmission in the mesolimbic system leads to the rewarding properties of alcohol. The mesolimbic DA system, which plays an important role in regulating reward and addiction, consists of DA neurons in the midbrain ventral tegmental area (VTA) that innervate the nucleus accumbens (NAc). It is believed that VTA DA neurons are inhibited by local gamma-aminobutyric acid (GABA) interneurons that express connexin-36 (Cx36) gap junctions (GJs). We have previously demonstrated that blocking Cx36 GJs suppresses electrical coupling between VTA GABA neurons and reduces ethanol intoxication and consumption suggesting that electrical coupling between …
Insulin And Ketones: Their Roles In Brain Mitochondrial Function, Sheryl Teresa Carr
Insulin And Ketones: Their Roles In Brain Mitochondrial Function, Sheryl Teresa Carr
Theses and Dissertations
The prevalence of both Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) is increasing worldwide, and the trends are unfortunately expected to continue. AD has recently been tied with mitochondrial dysfunction and insulin resistance, creating a mechanistic tie between AD and T2DM. Unfortunately, insulin resistance is often increased with aging and therefore, all individuals are at risk of brain mitochondrial dysfunction. Without proper mitochondrial function, the brain will degenerate, causing impaired cognitive function and reduced quality of life. The purpose of this study is two-fold: first, to understand the role of ceramides in insulin-induced brain mitochondrial dysfunction, and; second, …