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The Role Of Nr4a3 And Its Agonists In Skeletal Muscle Glucose Transport And Insulin Sensitivity, Qinglan Liu Jan 2013

The Role Of Nr4a3 And Its Agonists In Skeletal Muscle Glucose Transport And Insulin Sensitivity, Qinglan Liu

All ETDs from UAB

Insulin resistance plays a central role in the pathogenesis of Type 2 Diabetes (T2DM) and involves diminished stimulation of glucose transport in skeletal muscle. Improvements in insulin sensitivity are essential for both prevention and treatment of T2DM. However, the limitation of current medications highlights the need for alternative molecular regulators of insulin action and developing new insulin sensitizers. Our laboratory has initially identified roles for the orphan nuclear receptor NR4A3 in insulin-sensitization and stimulation of glucose transport. However, the cellular effect and downstream mechanisms of NR4A3 and its agonists (e.g. 6-mercaptopurine/6-MP) on insulin effector system in skeletal muscle remain unknown. …

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Investigation Of Death Receptor-5 Mediated Apoptosis And Inhibition Of Wnt/Ss-Catenin Signaling In Basal-Like Breast Cancer Stem Cells, Angelina Ix-Ik' Londono-Joshi Jan 2013

Investigation Of Death Receptor-5 Mediated Apoptosis And Inhibition Of Wnt/Ss-Catenin Signaling In Basal-Like Breast Cancer Stem Cells, Angelina Ix-Ik' Londono-Joshi

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Basal-like breast cancers (BLBC) display aggressive clinical behavior attributed to the presence of cancer stem cells (CSCs). TRA-8, a monoclonal antibody that binds specifically to TRAIL death receptor 5, preferentially induces apoptosis in BLBC subtype cells; however it is unknown if TRA-8 is also cytotoxic to the CSC population. Moreover, some BLBC cell lines are resistant to TRA-8, and overcoming resistance is critical for clinical translation of this therapy. One potential approach to overcome TRA- 8 resistance is to target the Wnt/ß-catenin pathway. LRP6 is a cell surface receptor that is an indispensable element of the Wnt/ß-catenin signaling pathway that …

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Epigenetic Regulation Of Kir4.1 In Normal And Pathological States: A Focus On Spinal Cord Injury, Sinifunanya Elvee Nwaobi Jan 2013

Epigenetic Regulation Of Kir4.1 In Normal And Pathological States: A Focus On Spinal Cord Injury, Sinifunanya Elvee Nwaobi

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Astrocytes are the most numerous cells in the brain and play a critical role in maintaining homeostatic extracellular potassium ([K+]e). This process is mediated, in part, by a glial-specific, inwardly rectifying potassium channel, Kir4.1. Pharmacological inhibition, knock down, or complete knock out of this channel results in astrocytes with increased membrane resistance, depolarized resting membrane potential, and altered extracellular potassium dynamics. Subsequent to the dysregulation of [K+]e, Kir4.1 knockout (KO) animals suffer from ataxia, seizures, and early postnatal death. Interestingly, Kir4.1 has long been characterized as a seizure susceptibility gene. The importance of Kir4.1 is further underscored by recent studies …

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New Mouse Models To Aid Studies Of The Role Of Primary Cilia In Limb Patterning And Bone Development, Amber Kathleen O'Connor Jan 2013

New Mouse Models To Aid Studies Of The Role Of Primary Cilia In Limb Patterning And Bone Development, Amber Kathleen O'Connor

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Hedgehog (Hh) signaling is required for many developmental processes, and causes several diseases and cancers. Described in chapter one below, vertebrate Hh sig-naling is dependent on the primary cilium (PC), a small organelle that extends from the surface of most mammalian cell types. A better understanding of how the PC modulates Hh signaling is important, as defects in the structure or function of PC result in severe human disorders termed the ciliopathies. For example, patients with Meckel-Gruber Syndrome have extra digits and neural tube defects, which are Hh both related pheno-types. In chapter two we sought to further understand the …

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Microevolution Of Capsule Synthesis Genes Contributes To Pneumococcal Capsule Diversity, Melissa Beth Oliver Jan 2013

Microevolution Of Capsule Synthesis Genes Contributes To Pneumococcal Capsule Diversity, Melissa Beth Oliver

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Streptococcus pneumoniae (pneumococcus) is an important human pathogen that expresses a capsular polysaccharide (PS) to shield underlying antigenic structures from complement-mediated opsonophagocytosis. Thus, capsular PS is the major virulence factor, the target of primary immune responses to pneumococcal infections, and the antigenic component of pneumococcal vaccines. Pneumococci have diverse capsular PS synthesis (cps) loci and express over 90 different capsule types. Such diversity helps pneumococci escape immune detection and adapt to changing environments. Recombination of cps genes has been recognized as the main driver of capsule diversity. However, we show point mutations in cps genes encoding glycosyltransferases can broaden enzymes' …

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Phospho-Erk And Amyloid Beta: Targets Of Estrogen In The Brain, Thomas Reed Peavy Jan 2013

Phospho-Erk And Amyloid Beta: Targets Of Estrogen In The Brain, Thomas Reed Peavy

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Estrogen replacement therapy (ERT) has been shown to improve memory function in menopausal women, but increases hormone sensitive cancers, prompting a more targeted investigation of estrogen's action in learning and memory to develop more targeted therapeutics. Estrogen improves performance on the novel object recognition task by increasing phosphorylation of extracellular signal-regulated kinase (pERK) within minutes in the hippocampus. Dr. Lori McMahon's lab showed that the improvement in novel object recognition can be seen 24 hours after subcutaneous injection of proestrous levels of estrogen (referred to as E24). Whether a corresponding increase in pERK occurs at the E24 time point had …

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The Genetic Complexity Of The Human Fc-Gamma Receptor 1q23 Locus And Its Relationship To Autoimmunity, Travis Samuel Ptacek Jan 2013

The Genetic Complexity Of The Human Fc-Gamma Receptor 1q23 Locus And Its Relationship To Autoimmunity, Travis Samuel Ptacek

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The human immune system must be able to adapt to a wide spectrum of invading pathogens in order to keep the human body alive. This variation includes directed recombination and mutation at the level of the individual and genetic variation and natural selection at the population level. A direct consequence of the adaptability of the immune system is autoimmunity: as the immune system adapts to a shifting spectrum of antigens, it can shift to self-antigens, and therefore attack the body and cause disease. Since genetic factors are part of this adaptability, they are also connected with autoimmune disease. SLE is …

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Rhodopsin Trafficking And Retinal Function, Nicholas Joseph Reish Jan 2013

Rhodopsin Trafficking And Retinal Function, Nicholas Joseph Reish

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The health and maintenance of rod photoreceptors depends on the high-fidelity vectorial transport of rhodopsin from its site of synthesis in the inner segment to its final resting place in the outer segment disks. Multiple molecular interactions play a role in this process, including the interaction of the small GTPase rab11a with rhodopsin that was first described in vertebrates in amphibians. We found that the interaction of the small GTPase rab11a and rhodopsin is conserved in mammalian retina. This interaction is direct, is abrogated by human disease-causing truncation mutations in rhodopsin, and does not depend on the nucleotide binding status …

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Studies Of Dna Gyrase Activity In Escherichia Coli And Salmonella Enterica Serovar Typhimurium., Nikolay Sergeyevich Rovinskiy Jan 2013

Studies Of Dna Gyrase Activity In Escherichia Coli And Salmonella Enterica Serovar Typhimurium., Nikolay Sergeyevich Rovinskiy

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Gyrase introduces negative supercoils into bacterial DNA. In balance with topoisomerase I, it contributes to the maintenance of constant negative DNA supercoiling. It was shown that in Escherichia coli negative supercoil density of pBR322 plasmid is higher than in Salmonella typhimurium. One of the possible explanations of this phenomenon is a difference of DNA gyrase activity between E. coli and S. typhimurium. We developed in vitro assay of gyrase activity which has shown that DNA gyrases of E. coli and S. typhimurium have the same supercoiling end point, but E. coli gyrase works slightly faster than the S. typhimurium enzyme. …

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Role Of Gsk3 In The Immunopathogenesis Of Eae, Amber Rowse Jan 2013

Role Of Gsk3 In The Immunopathogenesis Of Eae, Amber Rowse

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Lithium, a glycogen synthase kinase 3 (GSK3) inhibitor, ameliorates experimental autoimmune encephalomyelitis (EAE), the murine model of multiple sclerosis (MS) in different mouse models. However, the mechanism of lithium's attenuation of EAE and the role of GSK3 in these processes are currently unknown. IFN-g producing Th1 cells and IL-17-producing Th17 cells are both effector cells in MS and in EAE models. However, relapsing remitting MS patients segregate into Th1 or Th17 serum cytokine signatures and each is differentially responsive to IFN-ß therapy, a first line therapy for MS. Studies in this dissertation revealed a differential effect of lithium on Th1 …

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Surveying The Serum Proteome For Biomarkers Of Early-Stage Pancreatic Cancer, Michael Robert Ludwig Jan 2013

Surveying The Serum Proteome For Biomarkers Of Early-Stage Pancreatic Cancer, Michael Robert Ludwig

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SURVEYING THE SERUM PROTEOME FOR BIOMARKERS OF EARLY STAGE PANCREATIC CANCER MICHAEL ROBERT LUDWIG MICROBIOLOGY ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is a uniformly fatal disease due to its refractory nature to conventional therapies at the time of initial diagnosis. In order to in-crease the curative potential of surgical resection, early detection of organ-confined neoplasia is needed. Currently, no effective diagnostic tools are available to detect early-stage pancreatic ductal lesions termed pancreatic intraepithelial neoplasia (PanIN) or lo-cally invasive, organ-confined disease. One way to identify biomarkers that may be use-ful for the early detection of PDAC is through the study of the …

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The Phenotypic Expression Of Usp14 Deficiency Is Dependent Upon Genetic Background, Andrea Gail Marshall Jan 2013

The Phenotypic Expression Of Usp14 Deficiency Is Dependent Upon Genetic Background, Andrea Gail Marshall

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The ubiquitin proteasome system (UPS) plays a critical role in regulating a diversity of cellular processes that are essential to neuronal function, such as synaptic transmission, axon guidance, and neurite outgrowth. Dysfunctions of the UPS are linked with many neurodegenerative disorders, including motor neuron diseases like spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), although it is not known how UPS dysfunction contributes to disease pathology. The proteasome, an approximate 2.5 megadalton protein complex comprised of a 20S core particle and 19S regulatory particle, is the site of ubiquitin-mediated proteolysis in the cell. Recent studies have linked ubiquitin specific …

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The Role Of Palmitoylation And Other Post-Translational Modifications In Cftr Biogenesis, Michelle Mcclure Jan 2013

The Role Of Palmitoylation And Other Post-Translational Modifications In Cftr Biogenesis, Michelle Mcclure

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Post-translational modifications (PTMs) are important contributors to protein bio-genesis and function. CFTR in particular is known to be regulated by multiple PTMs, in-cluding glycosylation, phosphorylation, and ubiquitination. The functional significance and specific CFTR residues responsible for the majority of PTMs within CFTR are not known. The goal of this dissertation was to identify and characterize novel PTMs that influence wild-type and F508del CFTR. The study employed a combination of tandem and multiple reaction ion monitoring mass spectrometry to identify covalent side chain attachments. Analysis revealed the specific locations of numerous phosphorylated resi-dues, several sites of methylation, and more than twenty-five …

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Characterizing The Roles Of Il-11 And Cd68 In Breast Cancer Bone Metastasis, Erin Mills Mccoy Jan 2013

Characterizing The Roles Of Il-11 And Cd68 In Breast Cancer Bone Metastasis, Erin Mills Mccoy

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The molecular mechanisms regulating the preferential metastasis of breast cancer to bone have not been fully elucidated, but it is hypothesized that local conditions in the bone create an environment conducive to colonization by breast cancer cells and that the breast cancer cells interact directly with cells in the bone. In this dissertation, two goals were pursued: (1) to explore breast cancer secreted interleukin (IL)-11's role on osteoclast function and (2) investigate the expression and potential role of CD68 in breast cancer adhesion to bone. Higher rates of bone metastasis occur in human breast cancer tumors expressing IL-11, a cytokine …

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Intrinsic And Extrinsic Factors Required For Cd4 T Memory Cell Formation And Function, Sarah B. Mollo Jan 2013

Intrinsic And Extrinsic Factors Required For Cd4 T Memory Cell Formation And Function, Sarah B. Mollo

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CD4 T cells are central to the organization of the immune response through the secretion of cytokines that recruit and activate other immune cells. Following infection and pathogen control, the majority of the effector CD4 T cells undergo apoptosis, leaving a subset that persists and gives rise to the memory T cell pool. Upon encountering the same pathogen, memory CD4 T cells respond rapidly, providing enhanced protection from re-infection. What determines which effector CD4 T cells will survive is unclear; however, there are a number of factors both intrinsic to the cell as well as external signals from the environment …

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Phenotypic Analysis Of B Cells In Hla*B44 Positive Patients That Exhibit Common Variable Immunodeficiency And Recurrent Sino-Pulmonary Infections, Eva Szymanska Mroczek Jan 2013

Phenotypic Analysis Of B Cells In Hla*B44 Positive Patients That Exhibit Common Variable Immunodeficiency And Recurrent Sino-Pulmonary Infections, Eva Szymanska Mroczek

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Depressed serum immunoglobulin levels and recurrent sinopulmonary infections mark Common Variable Immune Deficiency (CVID). Many family members of CVID patients also suffer Recurrent Sino-Pulmonary Infection (RESPI) but have normal serum immunoglobulins. We identified HLAB44 positive identical female twins who suffer sinopulmonary infections and are discordant for CVID and RESPI. Flow cytometry subsets showed equivalent numbers of immature B cells (BC) in both twins, but lower numbers of transitional and mature BC in the CVID twin. Presented is an in-depth comparison of V (D) J gene usage, hydrophobicity, length, DH reading frame, and amino acid usage between µ H chain repertoires …

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Neuropathological Alterations In Alzheimer's Disease: An Up Close Look At Sympathetic Sprouting, Amy Renee Nelson Jan 2013

Neuropathological Alterations In Alzheimer's Disease: An Up Close Look At Sympathetic Sprouting, Amy Renee Nelson

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Pathological hallmarks of AD include neurofibrillary tau tangles, amyloid beta (Abeta) accumulation and cholinergic degeneration. Cholinergic degeneration can be mimicked in rats by lesioning cholinergic neurons in medial septum. Hippocampal cholinergic denervation disrupts retrograde transport of nerve growth factor (NGF), leading to its accumulation, which subsequently triggers sprouting of noradrenergic sympathetic fibers from the superior cervical ganglia into hippocampus. Dr. McMahon's lab previously reported that coincident with this sprouting, there is an increase in cholinergic innervation that correlates with a recovery of M1 muscarinic receptor dependent plasticity at CA3-CA1 synapses and visual cortex. These findings suggest that noradrenergic sympathetic sprouting …

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The Molecular Mechanisms Underlying Cardiac Hypertrophy Due To Volume Overload., Justin Andrew Barnes Jan 2013

The Molecular Mechanisms Underlying Cardiac Hypertrophy Due To Volume Overload., Justin Andrew Barnes

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Mitral regurgitation (MR) is a common form of heart disease, but there are no approved medical therapies for MR or other cardiovascular conditions associated with hemodynamic volume overload (VO) and eccentric remodeling. We have previously shown that a standard heart failure treatment, ß-adrenergic system blockade (ß-RB), improves function in animal models of VO and in MR patients without attenuating the adverse eccentric hypertrophy that occurs in conjunction with VO. This paradox highlights how poorly we understand eccentric remodeling of the heart, and a better understanding of the molecular mechanisms at work in VO must be obtained before we can develop …

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Adapter Based Strategies For Adenovirus Vector Retargeting To T Lymphocytes, Matthew S. Beatty Jan 2013

Adapter Based Strategies For Adenovirus Vector Retargeting To T Lymphocytes, Matthew S. Beatty

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Adenoviruses are the most commonly used gene therapy vector for cancer therapy clinical trials. While adenovirus has shown a great track record in a variety of cancer therapeutics it has not progressed as a vector system for the modification of T lymphocytes. One of the major roadblocks towards utilizing adenovirus for T cell therapy is the lack of coxsackie virus and adenovirus receptor on the cell surface of T cell lineages. Exploitation of alternative receptors has allowed adenovirus vectors to be utilized in a variety of cell types that native adenovirus type 5 cannot infect. Thus, retargeting adenovirus to an …

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O-Linked Beta-N-Acetylglucosamine (O-Glcnac) And The Mitochondrion, Christopher Calderon Jan 2013

O-Linked Beta-N-Acetylglucosamine (O-Glcnac) And The Mitochondrion, Christopher Calderon

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O-linked beta-N-acetylglucosamine (O-GlcNAc) is a dynamic and ubiquitous posttranslational modification of serine and threonine residues on nuclear and cytoplasmic proteins. O-GlcNAc has emerged as an important regulator of cellular processes such as cell signaling, transcription, translation, apoptosis, and cell cycle regulation, among others. O-GlcNAc is thought to be a contributor to pathologies such as hyperglycemia and insulin resistance. O-GlcNAc has been viewed as an indicator of cellular energy levels and is associated with diabetic complications under nutrient excess. Other studies have shown that a variety of stress stimuli increase the levels of protein O-GlcNAc in mammalian cells, and this increase …

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The Origin, Regulation, And Function Of Tbet In Effector Cd4 T Cells During Chronic Autoimmune Disease, Wen-I Yeh Jan 2013

The Origin, Regulation, And Function Of Tbet In Effector Cd4 T Cells During Chronic Autoimmune Disease, Wen-I Yeh

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Multiple Sclerosis (MS) is an autoimmune disease resulting from aberrant immune cells causing demyelination. We utilize the well-studied mouse model, experimental autoimmune encephalomyelitis (EAE), to decipher the underlying pathogenesis of MS. Effector CD4 T-cells play a critical role during EAE because the disease is induced by adoptively transferring myelin-specific CD4 T-cells into naïve mice. Classically, effector CD4 T-cells have been divided into distinct subsets based on their functional properties: Th1 cells produce IFNγ, Th2 cells secrete IL-4, IL-5, and IL-13, Th17 cells make IL-17A, IL-17F, IL-21, and IL-22, and regulatory T cells produce IL-10. Th1 cells were originally identified as …

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Experience-Dependent Synaptic Integration Of Adult-Generated Dentate Granule Cells, Jessica Hotard Chancey Jan 2013

Experience-Dependent Synaptic Integration Of Adult-Generated Dentate Granule Cells, Jessica Hotard Chancey

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The dentate gyrus (DG) contains neural stem cells that continually generate new neurons throughout life. The contribution of adult neurogenesis to hippocampal function is not well understood, but ablation or silencing of adult-generated neurons in the DG disrupts learning and memory, and neurogenesis is altered in many pathologies associated with impaired cognition including Alzheimer's Disease, epilepsy, and schizophrenia. Neurogenesis in the DG is a stepwise process in which neural stem cells leave the cell cycle and undergo an approximately two month long maturation process to form fully functional dentate granule cells (GCs) that are indistinguishable from those formed during development. …

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Identification Of Claudin-1 As An Entry Factor In Dengue Infection And Development Of A High Throughput Screening Assay For Antivirals Against Dengue Virus, Pulin Che Jan 2013

Identification Of Claudin-1 As An Entry Factor In Dengue Infection And Development Of A High Throughput Screening Assay For Antivirals Against Dengue Virus, Pulin Che

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Dengue virus (DENV) has become a huge public health concern around the world with no vaccine or antivirals available. More than one-third of the world's population is living in areas at risk of infection. To conquer the dengue disease, a better understanding of virus-host interactions and development of the appropriate therapeutic treatments are required. In this dissertation, we first broadly reviewed the factors involved in dengue viral entry and the role of tight junctions as a pathogen target. Second, we developed, optimized and validated a high throughput screening (HTS) assay for anti-dengue virus drug screening. Taking advantage of using live …

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Structure-Function Analysis Of Tyrosyl-Dna Phosphodiesterase I, Evan Comeaux Jan 2013

Structure-Function Analysis Of Tyrosyl-Dna Phosphodiesterase I, Evan Comeaux

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Tyrosyl-DNA phosphodiesterase I (Tdp1) functions to remove 3'phospho-DNA adducts, such as eukaryotic DNA Topoisomerase I (Top1) covalently bound to the DNA by a 3'phospho-tyrosyl bond. As member of the Phospholipase D superfamily Tdp1 contains two HxK(n)N motifs, each of which provide a catalytic histidine: one functioning as a nucleophile to bind the 3'phosphate and the other as a general acid/base to hydrolyze Tdp1's 3'phospho-histidyl bond. Mutation of the general acid/base catalytic histidine (Hisgab) to arginine has been implicated in the autosomal recessive neurodegenerative disease SCAN1. Further study of the yeast enzyme revealed that substitution of Hisgab in yeast Tdp1 to …

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Understanding The Function And Regulation Of Eukaryotic Release Factor 1, Erf1, Sara Elisabeth Conard Jan 2013

Understanding The Function And Regulation Of Eukaryotic Release Factor 1, Erf1, Sara Elisabeth Conard

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Translation termination is an essential eukaryotic process that facilitates the end of protein synthesis and mediates the release of the nascent peptide chain. Two release factors, eRF1 and eRF3, with the help of a ribosome recycling factor assist in this process. eRF1 and eRF3 form a stable complex through conserved regions in their C-terminal domains. The eRF1/eRF3 complex, along with GTP, is absolutely vital for efficient termination in vitro and in vivo. The role of eRF1 during translation termination is to recognize the stop codon located in the ribosome aminoacyl site, stimulate GTP hydrolysis of eRF3 and enable peptide release …

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Characterization Of The Mumps Virus Replicase, Robert Marsden Cox Jan 2013

Characterization Of The Mumps Virus Replicase, Robert Marsden Cox

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Negative strand RNA viruses (NSV) are unique because their nucleocapsids are used directly as the template for both transcription and replication. The viral genomic RNA is coated by the nucleoprotein (N) for the entirety of the NSV replication cycle. The viral polymerase, which is composed of the L and P proteins, can only recognize encapsidated RNA as the template for RNA synthesis. Our previous studies have solved the EM structure of the MuV N-RNA complex at 25Ņ. This structure revealed how the nucleocapsid is assembled and provides an initial model for examining how the viral polymerase may recognize the …

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Tgf-Ss And Erg In Intervertebral Disc Development, Megan Karen Cox Jan 2013

Tgf-Ss And Erg In Intervertebral Disc Development, Megan Karen Cox

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The intervertebral disc (IVD) is a fibrocartilaginous tissue that acts as a shock absorber between adjacent vertebrae in the spinal column. It is comprised of two parts, the inner jelly-like nucleus pulposus (NP) and the outer more fibrous annulus fibrosus (AF). Most IVD research has focused on the development of the NP, which is derived from condensations of the notochord involving sonic hedgehog (Shh) signaling. In contrast, very little is known about the molecular mechanisms underlying the specific development of the AF of the IVD. The AF is derived from the sclerotome, which is formed by the ventral half of …

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Selection And Evolution Of Pneumococci In Response To Conjugate Vaccines, Christina M. Croney Jan 2013

Selection And Evolution Of Pneumococci In Response To Conjugate Vaccines, Christina M. Croney

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Pneumococcal conjugate vaccines (PCVs) containing subsets of the >90 capsular polysaccharide antigens have been successful as a means of decreasing invasive and non-invasive pneumococcal disease worldwide. However, this success is limited to the specif-ic capsular serotypes against which PCVs are formulated and studies have reported the increase of nonvaccine serotypes. The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the United States in 2010 for the prevention of invasive pneumococcal disease (IPD) and otitis media and was released without efficacy data. In this study we set out to 1) determine potential efficacy for invasive and noninvasive pneumococcal disease and 2) …

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The Role Of Il-21 And Il-17 In Regulating Follicular T Helper Cells In Germinal Center Response Of Autoimmunity, Yanna Ding Jan 2013

The Role Of Il-21 And Il-17 In Regulating Follicular T Helper Cells In Germinal Center Response Of Autoimmunity, Yanna Ding

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Overreactivity of the germinal center (GC) is a central feature of autoantibody-mediated autoimmune diseases. Follicular T helper (Tfh) cells are the primary T helper subset that migrates to the incipient GC and forms close contacts with GC-B cells to promote GC formation and help GC-B cell differentiation, resulting in high-affinity antibody production. Increased levels of interleukin (IL)-21 and aberrant accumulation or function of Tfh cells have been associated with autoimmune disease severity in humans and lupus-prone mice. Follicular regulatory T (Tfr) cells are the regulatory T cell subset that also localizes in the GC and inhibits GC B cell differentiation. …

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Gabaergic Dysfunction In Huntington Disease, Sarah Elizabeth Dougherty Jan 2013

Gabaergic Dysfunction In Huntington Disease, Sarah Elizabeth Dougherty

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GABAergic neurons are responsible for regulation of neuronal signaling through inhibition. Alterations in the delicate balance of excitation and inhibition have been observed in many neurological disorders, including neurodegenerative diseases. Huntington disease (HD) is an autosomal dominant neurodegenerative disorder that is characterized by motor, psychiatric, and cognitive disturbances. As the hallmark movement pathology of HD is hyperkinesis it is intriguing to postulate that alterations in inhibition, and by extension within GABAergic cell networks, could be part of the pathogenesis of this disorder. In order to elucidate the role of GABAergic cell populations in HD we have used behavioral paradigms, molecular …

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