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Articles 31 - 60 of 137
Full-Text Articles in Neuroscience and Neurobiology
Viral Injection Of Rna Polymerase Ii-Interacting Protein Rprd2 In The Nucleus Accumbens Induces Anxiety-Like Behavior In Mice, Hannah E. Woolard
Viral Injection Of Rna Polymerase Ii-Interacting Protein Rprd2 In The Nucleus Accumbens Induces Anxiety-Like Behavior In Mice, Hannah E. Woolard
Theses and Dissertations
Anxiety and its related disorders have become increasingly prevalent as more awareness and acceptance of mental illnesses have come to fruition, especially in the light of the ongoing COVID-19 pandemic. Anxiety can affect anyone regardless of their age, sex, or social status and is currently the most commonly diagnosed mental illness worldwide (Bandelow & Michaelis, 2015). While there are several effective treatments available, the underlying brain mechanisms that cause anxiety are still largely unknown and further research continues to piece together the complex pathophysiology behind this disease. The use of laboratory animal models, such as mice, to induce and observe …
Theta Burst Brain Stimulation In Painful Diabetic Neuropathy Patients: Investigating Neural Mechanisms, Bhushan Thakkar
Theta Burst Brain Stimulation In Painful Diabetic Neuropathy Patients: Investigating Neural Mechanisms, Bhushan Thakkar
Theses and Dissertations
Chronic pain (CP) is a significant contributor to disability and disease burden globally. In 2019, approximately 50.2 million adults (20.4% of the US population) experienced chronic pain, contributing to $560-635 billion in direct medical costs. In addition, the worldwide prevalence of diabetes mellitus has reached epidemic proportions and is set to increase to 629 million by 2045. Almost 50% of patients with diabetes present with diabetic neuropathy (DN), and one in five patients with diabetes presents with painful DN (pDN) which is the most common cause of neuropathic pain (NP) in the US. Symptomatic treatment is the mainstay of management …
Traumatic Brain Injury-Induced Changes Of Immune/Inflammatory Response In The Context Of Predisposition Of Alzheimer’S Disease, Alexandra Pedin
Traumatic Brain Injury-Induced Changes Of Immune/Inflammatory Response In The Context Of Predisposition Of Alzheimer’S Disease, Alexandra Pedin
Theses and Dissertations
Alzheimer’s Disease (AD) is a progressive neurogenerative disease that affects millions globally. At this time there are no effective treatment options as the primary cause for AD is not fully understood. In addition to old age, genetic predisposition, and certain health conditions, traumatic brain injury (TBI) has been identified as a risk factor for AD. While the pathway that links TBI to AD is still largely unknown, the neuroinflammatory response to both conditions has been connected to the NLRP3 inflammasome. Due to its role in the innate immune system and proinflammatory cytokine mediation, the NLRP3 inflammasome could be a potential …
Chronic Adolescent Stress As A Predictive Factor For The Risk Of Developing Ptsd-Like Symptoms In Adulthood, Grace K. Young
Chronic Adolescent Stress As A Predictive Factor For The Risk Of Developing Ptsd-Like Symptoms In Adulthood, Grace K. Young
Theses and Dissertations
Post-traumatic stress disorder is a stress and trauma based psychological disorder that is defined by the DSM-IV as an anxiety disorder that affects approximately 7.8% of people in the United States. PTSD is when those who suffer a traumatic event have intense and distressing feelings, emotions, and memories for a prolonged period of time after the event. A prominent feature of PTSD is the impaired ability to properly extinguish a fear response after a dangerous trigger or stressor is no longer present, also known as safety learning. Stressors are threats perceived within the environment that activate a response within the …
The Injury-Induced Neurogenic Response And The Role Of Notch1 In Regulating This Process, Nicole M. Weston
The Injury-Induced Neurogenic Response And The Role Of Notch1 In Regulating This Process, Nicole M. Weston
Theses and Dissertations
Traumatic Brain Injury (TBI) is a prevalent problem with an estimated 5 million people suffering from chronic cognitive impairments long after the injury. Following TBI there is a series of pathophysiological changes in the brain including neurogenesis, an important response linking endogenous repair and regeneration. The dentate gyrus (DG) of the hippocampus is a primary neurogenic region within the adult brain where neural stem and progenitor cells (NS/NPCs) reside. Studies using rodent models have shown that cognitive recovery after TBI is associated with new neurons generated from the DG. Thus far, in studies examining post-injury neurogenesis, the regulatory mechanisms, functional …
Anti-Angiogenic Effects Of Chemotherapeutic Agents And Their Enhancement With Ot-515 And S-Nach, Shimaa Adel Heikal
Anti-Angiogenic Effects Of Chemotherapeutic Agents And Their Enhancement With Ot-515 And S-Nach, Shimaa Adel Heikal
Theses and Dissertations
Chemotherapeutic agents have been used for the treatment of numerous types of tumors with great success. Cisplatin and Doxorubicin are among the well-known chemotherapeutic drugs that showed efficacy against various types of cancers. However, cell resistance and major side effects like chemotherapy-induced peripheral neuropathy (CIPN) are limiting factors in using these compounds. Using a combination or adjuvant compounds with anti-angiogenic effects is one of the strategies suggested to decrease resistance or ameliorate chemotherapeutic toxicity. The present study investigated the anti-angiogenic effects of Cisplatin and Doxorubicin alone and combined with Sulfated non-anticoagulant heparin (S-NACH), a low molecular weight heparin LMWH that …
Effects Of The Antidepressant Drug Vortioxetine On Ventral Pallidal Neuronal Activity, Respiration, And Heart Rate In The Rat, Piper Rogers
Effects Of The Antidepressant Drug Vortioxetine On Ventral Pallidal Neuronal Activity, Respiration, And Heart Rate In The Rat, Piper Rogers
Theses and Dissertations
Major Depressive Disorder (MDD) is a mental illness that affects millions of people worldwide. People diagnosed with MDD are often prescribed antidepressant drugs. Most antidepressants increase levels of serotonin (5-hydroxytryptamine, 5-HT) in the synapses between neurons. Selective-serotonin reuptake inhibitors (SSRIs), one class of antidepressants, do this by inhibiting the reuptake of serotonin released into the synapse. Serotonin neurons from the brainstem raphe nuclei affect a wide range of areas throughout the brain. Among these areas is the ventral pallidum (VP), located in the basal forebrain. Citalopram, an SSRI, has been found to increase the firing rate of action potentials of …
Physiological Consequences Of Neuromodulation And The Cellular Properties That Underlie Them, Margaret Louise Demaegd
Physiological Consequences Of Neuromodulation And The Cellular Properties That Underlie Them, Margaret Louise Demaegd
Theses and Dissertations
Neuronal activity is a product of more than the underlying neuronal connections. Modulatory influences like changes in the animal’s environment, the animals physiological state, or the release of neuromodulators can dramatically alter neuronal activity. Modulatory influences can be beneficial for the animal because they are a source of neuronal and behavioral plasticity, and they can provide neuronal circuits with the robustness needed to continue to function in new conditions, states, or tasks.However, malfunctions of the modulatory system can disrupt neuronal activity and lead to pathologies. Predicting how modulatory influences will alter neuronal activity is challenging because the underlying cellular and …
Rna Splicing In Neuron Physiology And Neurodegenerative Diseases, Md Faruk Hossain
Rna Splicing In Neuron Physiology And Neurodegenerative Diseases, Md Faruk Hossain
Theses and Dissertations
Gene expression is regulated at multiple levels, including transcription, RNA editing, pre-mRNA splicing, mRNA export, translation, and posttranslational modifications. Alternative splicing is a process by which exons can be included or excluded, giving rise to multiple mRNA isoforms from the same transcript. Alternative splicing is an important mechanism in developmental, tissue- and cell-specific control of gene expression, and it is key for expanding proteomic diversity and complexity from a limited number of genes. Moreover, more than 95% of multiexon genes undergo alternative splicing in humans, and about half of all disease-causing point mutations in humans affect pre-mRNA splicing, including neurological …
Alpha-Synuclein Multimerization Is Dependent On Structural Characteristics Of Repeated Ktkegv Regions, Benjamin Ira Rosen
Alpha-Synuclein Multimerization Is Dependent On Structural Characteristics Of Repeated Ktkegv Regions, Benjamin Ira Rosen
Theses and Dissertations
Parkinson’s disease (PD) is the most common movement disorder and is characterized by neuronal loss and the presence of Lewy bodies in dopaminergic neurons of the substantia nigra pars compacta. PD is a chronic, progressive, and irreversible neurodegenerative disorder associated with the selective loss of dopaminergic neurons. Initially described in an Ayurvedic medical treatise and Galen’s writings, and later by James Parkinson in 1817, the most common symptoms of PD are resting tremors, abnormal posture and gait, and muscle rigidity. Approximately 1 million people are living with PD in the United States and worldwide estimates are between 7 and 10 …
Microrna Regulation And Cellular Proteostasis In Parkinson's Disease, Alberim Kurtishi
Microrna Regulation And Cellular Proteostasis In Parkinson's Disease, Alberim Kurtishi
Theses and Dissertations
Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disorder predominately affecting the aging population. It is the second most common neurodegenerative disorder after Alzheimer’s disease (AD) affecting over 1 million individuals in the US alone. Recent studies have tried to understand the exact nature in which healthy neurons transition to a degenerative state in PD. There are a multitude of combinatory factors that can lead to the development of PD including environmental factors, genetic factors, and aging. The majority of PD cases are sporadic in nature, however familial cases account for 5-10% of total PD cases world-wide. The hallmark …
Glucocorticoid Receptor Dysregulation Underlies 5-Ht2a Receptor-Dependent Synaptic And Behavioral Deficits In A Mouse Neurodevelopmental Disorder Model, Justin M. Saunders
Glucocorticoid Receptor Dysregulation Underlies 5-Ht2a Receptor-Dependent Synaptic And Behavioral Deficits In A Mouse Neurodevelopmental Disorder Model, Justin M. Saunders
Theses and Dissertations
Schizophrenia is a severe neuropsychiatric disorder that presents with diverse symptoms, some of which remain resistant to treatment. Increased risk of neurodevelopmental disorders such as schizophrenia has been observed following gestational infection in humans, leading to development of maternal immune activation (MIA) animal models. Increased density of the serotonin 5-HT2AR receptor (5-HT2AR), the primary target of hallucinogenic drugs and a key target of atypical antipsychotics, has been observed in postmortem antipsychotic-free prefrontal cortex samples from schizophrenia subjects, a change reflected in frontal cortex of adult MIA offspring. To model MIA, we administered 20 mg/kg i.p. of the viral mimetic poly-(I:C) …
Novel Roles Of Yy1 In Astrocytes, Karli A. Mockenhaupt
Novel Roles Of Yy1 In Astrocytes, Karli A. Mockenhaupt
Theses and Dissertations
Astrocytes tile the entire central nervous system, are diverse across brain regions, and perform specialized functions fine-tuned for their neuronal circuit. Initially, astrocyte heterogeneity is generated through intrinsic programs specified by their progenitors. Then, as astrocyte mature, they are specialized by region-specific communication with surrounding cells. The molecular programs that regulate this diversity and allow for the accommodation to the needs of the local environment remains elusive. We explored a ubiquitously expressed zinc finger transcription factor, Yin Yang 1 (YY1), that both activates and represses transcription by regulating loops of active chromatin. This report describes the diverse functions of astrocytic …
Muscarinic Excitation Of Dopamine Neurons In The Ventral Tegmental Area Via Activation Of A Trpc-Like Cation Conductance, Yu Tzu Chen
Theses and Dissertations
Dopaminergic (DA) neurons in the ventral tegmental area (VTA) play a crucial role in reward and motivational behaviors, including the development of drug addictions. VTA DA neurons receive excitatory cholinergic inputs from the mesopontine tegmentum. Blockage of the M5 muscarinic receptor in DA neurons has been shown to attenuate drug-induced DA release and abuse-related behaviors, but the molecular mechanism is unknown. In this study, experiments were designed to identify the electrophysiological effects of muscarinic agonism in the modulation of action potential kinetics and firing patterns in VTA DA neurons of mice. Pharmacology of the muscarinic receptor-evoked current was also characterized. …
Investigating Cannabinoid Type-1 Receptor (Cb1r) Positive Allosteric Modulators (Pams) In Mouse Models Of Overt Cannabimimetic Activity, Subjective Drug Effects, And Neuropathic Pain, Jayden Elmer
Theses and Dissertations
Chronic pain affects between 20 and 30 percent of the adult population in western countries and represents a wide array of specific etiologies (Berge, 2011). Neuropathic pain secondary to traumatic nerve injury, chemotherapeutic toxicity, or diseases (e.g., diabetes mellitus) is often refractory to conventional analgesics, with patients receiving less than 50% pain relief compared to placebo (Finnerup et al. 2010). The endocannabinoid system has shown potential as a therapeutic target for neuropathic pain wherein CB1 agonism via administration of exogenous agonists or pharmacological blockade of endocannabinoid catabolic enzymes exhibits efficacy in reversing allodynia in the chronic constriction injury (CCI) model …
Interclass Gpcr Heteromerization Affects Localization And Trafficking, Rudy Toneatti
Interclass Gpcr Heteromerization Affects Localization And Trafficking, Rudy Toneatti
Theses and Dissertations
Class A serotonin (5-hydroxytryptamine) 2A (5-HT2AR) and class C metabotropic glutamate 2 receptors (mGluR2) are seven transmembrane receptors (7TMRs or G protein-coupled receptors – GPCRs) involved in multiple neuropsychiatric disorders including schizophrenia. Previous findings from our laboratory reported that 5-HT2AR and mGluR2 are dysregulated in the prefrontal cortex of patients suffering from this psychiatric condition, although 5-HT2AR’s expression was recovered in antipsychotic-medicated patients. Genome-wide association studies on schizophrenia reported that endosomal trafficking that regulates cell surface abundance of another 7TMR implicated in this disease (dopamine D2 receptor) can be altered. Ligand-activated receptors, including the …
Evaluating Neuromuscular Function Of The Biceps Brachii After Spinal Cord Injury: Assessment Of Voluntary Activation And Motor Evoked Potential Input-Output Curves Using Transcranial Magnetic Stimulation, Thibault Roumengous
Theses and Dissertations
Activation of upper limb muscles is important for independent living after cervical spinal cord injury (SCI) that results in tetraplegia. An emerging, non-invasive approach to address post-SCI muscle weakness is modulation of the nervous system. A long-term goal is to develop neuromodulation techniques to reinnervate (i.e. resupply nerve to) muscle fiber and thereby increase muscle function in individuals with tetraplegia. Towards this goal, developing monitoring techniques to quantify neuromuscular function is needed to better direct neurorehabilitation. Assessment of voluntary activation (VA) is a promising approach because the location of the stimulus can be applied cortically using transcranial magnetic stimulation (TMS) …
The Role Of Glt-1 Signaling In Oligodendrocytes During Development And Myelin Repair, Elizabeth Thomason
The Role Of Glt-1 Signaling In Oligodendrocytes During Development And Myelin Repair, Elizabeth Thomason
Theses and Dissertations
The differentiation of oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes (OLGs) requires an increase in the complexity of process morphology, alterations in membrane trafficking, and the production of myelin proteins. Branching and process extension have already been shown to follow glutamate signaling through OLG-expressed excitatory amino acid transporters (EAATs), mostly via GLT-1. It is of note that glutamate homeostasis often goes awry in multiple sclerosis (MS), the main demyelinating disease in humans. Thus, we have sought to gain an understanding of the role that GLT-1 plays under the myelination and remyelination conditions that arise during natural development of OLGs and …
Cytotoxic Analysis Of Old Drugs: New Drugs For Alzheimer’S Disease, Sebastian Yumiseba
Cytotoxic Analysis Of Old Drugs: New Drugs For Alzheimer’S Disease, Sebastian Yumiseba
Theses and Dissertations
Microglia are the resident immune cells of the CNS and constitute about 10% of all cells in the CNS. They have a vital role in Alzheimer’s pathogenesis as either cytotoxic or neuroprotective. Recent efforts are being put into repurposing drugs to target the microglia to treat Alzheimer’s disease.
Expression Analyses Of Hippocampal And Cortical Proteins In A Rat Model For Alzheimer’S Disease, Rangon Islam
Expression Analyses Of Hippocampal And Cortical Proteins In A Rat Model For Alzheimer’S Disease, Rangon Islam
Theses and Dissertations
Currently, Alzheimer’s disease (AD) has no cure. Using a rat AD model, we identified aberrantly expressed proteins during pre-pathology as potential biomarkers. The expression of certain biomarkers was reversed by diazoxide, a repurposed hypertension drug. These results suggest that drug repurposing at an early stage of AD has therapeutic potential.
Assessing The Role Of Planar Cell Polarity Protein Ptk7 In Axon Pathfinding Of Spinal Commissural Neurons, Joseph Paul Miano
Assessing The Role Of Planar Cell Polarity Protein Ptk7 In Axon Pathfinding Of Spinal Commissural Neurons, Joseph Paul Miano
Theses and Dissertations
Axon pathfinding is a fundamental step that establishes the vast networks of the nervous system. Understanding this process is important because disruptions to these neural networks can impair quality of life. During axon pathfinding, an axon’s growth cone comes in contact with a variety of secreted chemotropic signaling cues that control growth cone behavior through activation of signal transduction pathways which cause changes to the cytoskeleton. One such pathway is the Planar Cell Polarity (PCP) signal transduction pathway that responds to gradients of non-canonical Wnt ligands. PCP has a well-known role in axon pathfinding, including axon pathfinding in the spinal …
Ndrg1 And Myelin-Related Disease: Alcoholism And Chemotherapy-Induced Neuropathy, Guy Harris
Ndrg1 And Myelin-Related Disease: Alcoholism And Chemotherapy-Induced Neuropathy, Guy Harris
Theses and Dissertations
Alcohol use disorder (AUD) is a prevalent neuropsychiatric disease with profound health, social, and economic consequences. With an estimated 50% heritability, identifying genes that engender risk and contribute to the underlying neurobiological mechanisms represents an important first step in developing effective treatments. Gene expression studies are an important source of candidate genes for studying AUD, providing windows into the molecular machinery engaged by the brain in response to ethanol. Our laboratory has implicated N-myc down-regulated gene 1 (Ndrg1) as a potential candidate gene that modulates ethanol-induced changes in myelin-related gene expression and acute sensitivity to ethanol. Analysis of …
Focal Augmentation Of Somatostatin Interneuron Function And Subsequent Circuit Effects In Developmentally Malformed, Epileptogenic Cortex, Nicole Ekanem
Theses and Dissertations
Drug-resistant epilepsy (DRE) is a common clinical sequela of developmental cortical malformations such as polymicrogyria. Unfortunately, much remains unknown about the aberrant GABA-mediated circuit alterations that underlie DRE's onset and persistence in this context. To address this knowledge gap, we utilized the transcranial freeze lesion model in optogenetic mice lines (Somatostatin (SST)-Cre or Parvalbumin (PV)-Cre x floxed channelrhodopsin-2) to dissect features of the SST, PV, and pyramidal neuron microcircuit that are potentially associated with DRE. Investigations took place within developmental microgyria’s known pathological substrate, the adjoined and epileptogenic paramicrogyral region (PMR). As well, microcircuit relationships within the previously unexplored range …
Validation Of Ninein As An Ethanol-Related Quantitative Trait Gene: Reassessment, Design, And Functional Validation Of Reference Genes For Qpcr Analysis Of Brain Tissue In Mice, Jessica L. Jurmain
Validation Of Ninein As An Ethanol-Related Quantitative Trait Gene: Reassessment, Design, And Functional Validation Of Reference Genes For Qpcr Analysis Of Brain Tissue In Mice, Jessica L. Jurmain
Theses and Dissertations
The increasing use of quantitative real-time polymerase chain reaction (qPCR) as a method for quantifying gene expression has led to an increased demand for standardization of data analysis methods to ensure accurate reporting and robust, reproducible results. The exponential nature of qPCR amplification results in the potential magnification of what are usually very small sources of error. Relative gene expression calculations circumvent this issue by normalizing target gene expression data to within-sample expression of a previously validated, stably expressed reference gene or genes. Multiple studies discussed herein have found that qPCR data are more reliable and reproducible when multiple reference …
A Study On The Mechanism Of Clp290 Restoration Of Kcc2 And Neuroprotection After Traumatic Brain Injury, Ekaterina Stepanova
A Study On The Mechanism Of Clp290 Restoration Of Kcc2 And Neuroprotection After Traumatic Brain Injury, Ekaterina Stepanova
Theses and Dissertations
The research of this thesis investigated the mechanism of action for the therapeutic compound CLP290, which our laboratory has previously demonstrated to reverse degradation of the protein potassium-chloride co-transporter 2 (KCC2) and restore neuronal function following modeled traumatic brain injury (TBI) in the rat. The loss of membranous KCC2 from the plasma membrane after TBI worsens the excitation/inhibition imbalance common in neurotrauma. Addressed here were the specific aims to: 1) assess that CLP290 treatment restores the functional oligomeric form of KCC2 to the neuronal plasma membrane as necessary to provide chloride homeostasis; 2) investigate the signaling mechanism by which CLP290 …
How Does Eye Movement Desensitization And Reprocessing (Emdr) Work? An Examination Of The Potential Mechanisms Of Action, Sara Forster
How Does Eye Movement Desensitization And Reprocessing (Emdr) Work? An Examination Of The Potential Mechanisms Of Action, Sara Forster
Theses and Dissertations
A mounting body of evidence suggests that Eye Movement Desensitization and Reprocessing therapy (EMDR) is successful in reducing the impact of posttraumatic symptoms. Although the exact mechanisms of action remain unknown, theories from the psychological to the neuroscientific continue to emerge, expand, and evolve. This study will examine four of the most prominent theories to date and weigh the evidence for and against each one. It will also review, compare, and contrast the theories, evaluate the research supporting each one, and propose the most likely explanation for EMDR's success given the state of the research. Neurobiological mechanisms and correlates as …
Epigenetic Alterations At Synaptic Plasticity Genes In A Genetically Heterogeneous Rat Model Of Neuropsychiatric Disorders, Doan M. On
Theses and Dissertations
Sensorimotor gating impairments are observed across a range of neuropsychiatric conditions. The prepulse inhibition of the acoustic startle response (PPI) is a validated measure of sensorimotor gating. Genetic and pharmacological manipulations in rodents have shown PPI is regulated by specific brain monoaminergic systems. Using genetically heterogeneous NIH-HS rats, we stratified individuals by %PPI. In low PPI animals, we observed elevated mRNA levels of certain neurotransmitter receptors, including metabotropic glutamate receptor Grm2, dopamine receptors Drd1 and Drd2, serotonin receptors Htr1a and Htr2a, and scaffolding protein Homer1, in the frontal cortex (FC) and striatum (STR). We found Drd2 …
Role Of Clic4 And The Synaptic Transcriptome In The Behavioral And Molecular Neurobiology Of Ethanol, Rory M. Weston
Role Of Clic4 And The Synaptic Transcriptome In The Behavioral And Molecular Neurobiology Of Ethanol, Rory M. Weston
Theses and Dissertations
Alcohol use disorder (AUD) is a prevalent neuropsychiatric disease with profound health, social, and economic consequences. With an estimated 50% heritability, identifying genes that engender risk and contribute to the underlying neurobiological mechanisms represents an important first step in developing effective treatments. Gene expression studies are an important source of candidate genes for studying AUD, providing windows into the molecular machinery engaged by the brain in response to ethanol. Published studies have identified chloride intracellular channel 4 (Clic4) as an ethanol-regulated gene in brain capable of modulating sensitivity to sedation in multiple species. The functions of Clic4 are …
Effects Of Gestational Ozone Exposure On Privileged Placental And Brain Barrier Integrity, Alexander I. Hamm
Effects Of Gestational Ozone Exposure On Privileged Placental And Brain Barrier Integrity, Alexander I. Hamm
Theses and Dissertations
Ambient outdoor ozone, a common of component of photochemical smog and urban air pollution, is linked to various neurological and vascular pathologies. Its immediate reaction with lung surfactant after inhalation results in complete reactivity of the gas, with no active ozone passing into circulation. This indicates the presence of secondary and tertiary mediators in ozone-related systemic pathologies after pulmonary insult. In vasculature, ozone exposure is associated with an acute hypertensive phenotype apparent at least 24 hours after dose, such as experienced on a hot summer afternoon in a large metropolitan area like Los Angeles or Mexico City. However, the effects …
Lpa Receptors Modulate Gene Expression During Oligodendrocyte Differentiation, Samantha A. Spencer
Lpa Receptors Modulate Gene Expression During Oligodendrocyte Differentiation, Samantha A. Spencer
Theses and Dissertations
LPA, produced by the lysoPLD activity of ATX, binds its cognate receptors and regulates the development of multiple brain cells, including oligodendrocytes (OLGs). OLGs progress through a lineage from precursor (OPC) to early OLG to immature OLG, until finally the cells mature and enwrap axons to enable saltatory conduction and provide trophic support. The studies in this dissertation characterized the receptors LPA4 and LPA6 as inhibitors of OPC differentiation. Western blot analysis of MS patient lesion tissue found a negative correlation between ATX levels and levels of LPA4 and LPA6. A previously created homology model for LPA4 was used to …