Neuroscience and Neurobiology Commons^™

Effect Of Reduced Cardiomyocyte O-Glcnacylation On The Expression And Activity Of The Cardiac Voltage-Gated Sodium Channel, Chiagozie Dawn Bede Paul-Onyia

Browse all Theses and Dissertations

Abnormal glycosylation can impact cardiac proteins, affecting signaling, contraction, and metabolism, which leads to compromised cardiac function. O-GlcNAcylation, the only form of intracellular glycosylation, involves adding a single GlcNAc molecule to proteins via enzymes: O-GlcNAc Transferase (OGT) for addition and O-GlcNAcase (OGA) for removal. The Ednie/Bennett lab has previously demonstrated that in both chronic (OGT KO) and acute (OGT inhibition) models of reduced cardiomyocyte O-GlcNAcylation, a disruption of Ca2+ homeostasis occurs. This study delved into the cardiac voltage-gated sodium channel (NaV 1.5) in these models. NaV 1.5 expression was analyzed through western blotting and immunocytochemistry, while its functional activity was …

Repeated Occupational-Level Exposure To The Pesticide Malathion Leads To Neuronal Atrophy In The Dorsal Root Ganglion, Arian K. Mcneil

Browse all Theses and Dissertations

Environmental exposure to organophosphate (OP) pesticides, such as malathion, is a risk factor for neuropathy and neurodegeneration. Toxic levels of OPs irreversibly inhibit acetylcholinesterase (AchE) activity, leading to acute paralysis and even death as the neurotransmitter acetylcholine accumulates at cholinergic synapses. In addition, there is compelling evidence that repeated low-level “occupational-like” exposure to OPs is associated with somatosensory defects but the cellular mechanisms for this effect are unclear. We show sensory neuron cell size in the dorsal root ganglia is significantly reduced in rats exposed to occupational level malathion. However, co-administration of a reversible AchE inhibitor, galantamine, prevented this effect.

Brain Glycogen – Beyond Energy Storage In Glycogen Storage Diseases, Kia H. Markussen

Theses and Dissertations--Molecular and Cellular Biochemistry

Glycogen is a carbohydrate molecule that is traditionally viewed as a convenient and easily accessible energy storage form of glucose. However,emerging evidence supports the role of glycogen as more than a glucose storage form. During the last 20 years, glycogen has been shown to play pivotal roles in learning and memory, signaling events, viscosity, protein glycosylation, and be acritical hallmark in devastating diseases. Not only, does glycogen play a role as an energy substrate and critical metabolite during energy deprivation, glycogen is central for neurotransmitter homeostasis, tumor initiation, and ontributes to proper protein glycosylation in the brain. In this work, …

Ultrastructural Correlates Of Axons And Synapses Belonging To Different Circuits In Ferret Primary Visual Cortex, Anjelique Sawh

Dissertations and Theses

The goal of this study was to determine differences in distinctive layers of mammalian primary visual cortex through analysis of their ultrastructural characteristics. Characterizing brain circuitry using 3-dimensional reconstruction of electron microscopy images, and subsequent ultrastructural analysis of axonal populations provides us with a better understanding of the connectivity of the neural circuits. By quantifying ultrastructural differences in axonal processes such as synaptic densities, types of synapses and their post-synaptic densities (PSDs), mitochondrial volumes, synaptic vesicle aggregates, dendritic targets, and bouton volumes, we aimed to understand whether differences in anatomical specializations among different cortical layers could underlie differences in function …

Tdcs Effects On Synaptic Plasticity And Motor Skill Learning, Forouzan Vasheghani Farahani

Dissertations and Theses

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that involves the application of low-intensity constant current to the brain through electrodes placed on the scalp. Its potential to enhance brain function and treat brain-related disorders has led to its increasing popularity due to its safety, simplicity, and affordability. However, its effectiveness remains a topic of debate.

Machine Learning Approach To Predict Tdcs-Induced Electric Current In The Human Brain, Chikako Olsen

Dissertations and Theses

Background: Transcranial direct current stimulation (tDCS) is a promising non-invasive method for treating neurological and psychiatric disorders and enhancing cognitive function. However, the underlying mechanisms of tDCS are not fully understood, and there is no ground truth for determining, non-invasively, where in the brain tDCS electrical currents flow. At the same time, effective neuronal engagement from tDCS requires accurate localization of the induced currents to specific brain target regions. Machine Learning (ML) has the potential to significantly improve the accuracy and precision of tDCS current prediction. This study aims to develop a novel approach using ML to predict the location …

Effects Of Hiv-1 Tat And Opiates On Gene Regulation Of Oligodendrocyte Lineage Cells: Identification Of Myrf As A Novel Target, Kelly M. Flounlacker

Theses and Dissertations

HIV-associated neurocognitive disorders remain pervasive even with increased efficacy/use of antiretroviral therapies. Opioid use/abuse among HIV+ individuals is documented to exacerbate deficits. White matter (WM) alterations (myelin pallor, volume/structural) detected by diffusion tensor imaging, are common observations in HIV+ individuals. Using transgenic mice expressing HIV-1 Tat, we examined effects of 2-6 weeks of Tat/morphine exposure on WM using genomic/biochemical methods. RNA sequencing of striatal tissue after 2-weeks revealed robust changes in mRNAs associated with oligodendrocyte populations/myelin integrity, including Transferrin, Ndrg1, and myelin regulatory factor (Myrf/Mrf), an oligodendrocyte-specific transcription factor involved in differentiation/maturation. Immunoblots conducted after 6-weeks exposure in …

Unraveling The Consequence Of Adult Onset Sulfatide Depletion: Its Implications In Myelin And Axonal Heath In The Context Of Neurodegenerative Disease, Elizabeth Dustin

Theses and Dissertations

Multiple Sclerosis is an immune mediated disease of the CNS. MS is diagnosed through detection of demyelinated regions. However, recent studies demonstrate that Normal Appearing White Matter (NAWM) contains substantial pathology. One such pathology observed in the NAWM is the reduction of sulfatide. The proper stoichiometry of lipids in myelin acts to maintain rapid conduction velocity, provide trophic support to the neuron, and protect the axon from degeneration. We previously characterized a mouse lacking sulfatide’s synthesizing enzyme, CST through constitutive gene disruption and demonstrate that sulfide is required for proper stability of the myelin sheath. However, since MS is typically …

Interactions Between Hiv And Opioids On Antiretroviral Accumulation, The Blood Brain Barrier, And The Inflammatory Response In The Brain., Kara Rademeyer

Theses and Dissertations

The complex mechanisms related to HIV infection, neurodegeneration, and chronic neuroinflammation collectively describe neuroHIV (Hauser et al. 2007; Chang et al. 2014; Smith et al. 2014). Specifically, opioid abuse, poor penetration of antiretroviral (ARV) drugs, chronic inflammation and neuronal injury/degeneration are all implicated in neuroHIV (Fantuzzi et al. 2003; Letendre et al. 2004; Verani et al. 2005; Duncan and Sattentau 2011; Hong and Banks 2015; Simoes and Justino 2015; Olivier et al. 2018; Murphy et al. 2019; Osborne et al. 2020). For the first time, we demonstrate that morphine, fentanyl, and methadone in vivo alter the brain accumulation of ARVs, …

Epithelial Membrane Protein 3 (Emp3b) Is A Novel Regulator Of Sympathetic Nervous System Development In Zebrafish., Jessica M. White

Theses and Dissertations

Notable progress has been made in understanding the development of the neural crest (NC). Neural crest cells (NCCs) can be divided into 4-5 subpopulations. A major lineage among trunk NC derivatives are sympathoadrenal (SA) cells, which give rise to the sympathetic nervous system (SNS). Trunk NCCs follow a ventromedial migration pathway where signals derived from the dorsal aorta instruct migrating NCCs to a SA cell fate. Defects in NC development can result in syndromes known as neurocristopathies. Neuroblastoma is one of the most common forms of pediatric cancer affecting nearly 800 infants each year in the United States (Takita et …

The Impact Of Hiv-1 Tat And Morphine On Spatial Distribution Of Drugs In The Brain., Austin M. Jones

Theses and Dissertations

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, the central nervous system (CNS) remains affected by the virus. Approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND) or neuroHIV. Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, viral replication, and potentially altering the antiretroviral concentrations within the brain.

Using a transgenic mouse that expresses the HIV-1 Tat protein, we examined the effects of Tat and morphine on antiretroviral accumulation and distribution and the effects of Tat on morphine accumulation within the brain using infrared matrix-assisted laser desorption electrospray ionization with mass spectrometry imaging (IR-MALDESI-MSI). …

Mechanistic Insight Into Traumatic Brain Injury Induced Neuronal Membrane Disruption: Cathepsin B Relocalization And A Neun Negative Cortical Neuron Subpopulation, Martina L. Hernandez

Theses and Dissertations

Traumatic brain injury (TBI) is a mechanical insult to the head that leads to brain damage and, in turn, causes long-term sensory, motor, cognitive, and affective dysfunction. Diffuse pathologies seen following such injury are associated with these life-altering outcomes that impact the daily lives of TBI survivors. The diffuse pathology that this body of work focuses on is neuronal membrane disruption; it is characterized by increased permeability of the neuron’s plasma membrane. Moreover, our lab had previously found that membrane disruption is exacerbated with intracranial pressure (ICP) elevation. We set out to measure the duration of membrane disruption following injury …

A State Space Modeling Approach To Eeg Artifact Removal, Patrick B. Rafael

Graduate Research Theses & Dissertations

In this work, a state space modeling approach is applied to an Electroencephalography(EEG) recording for the purpose of artifact removal, and is compared against Independent Components Analysis (ICA), the current gold standard. Issues of model identifiability are touched on, and Hamiltonian Monte Carlo (HMC) is used to estimate a linear non-Gaussian state space model. Results show that estimating such a model is a nontrivial matter, and the full utility of the state space approach remains to be demonstrated.

Glyphosate And Dopaminergic Neurotoxicity: Herbicide Impacts On Parkinson's Disease Development, Lojy Hozyen

UROP Posters

Nearly one million individuals in the United States are living with Parkinson’s disease (PD). In the past two decades, the death rate from PD has risen by about 63 percent in the United States. Major findings have been made in the past five years about the potential impact of glyphosate (N-(phosphonomethyl) glycine) exposure on the onset of PD symptoms. The purpose of this meta-analysis is to provide a compiled update on the chemical and biological alterations that glyphosate imposes on the human brain. A meta-analysis was conducted to create a quantitative estimate of the connection between PD and glyphosate. Findings …

Factors Related To The Perceptions Of Academic Honesty Among Campus-Based And Online Undergraduate Students, Robert Defranco

Walden Dissertations and Doctoral Studies

Academic dishonesty poses a challenge for the online and campus-based learning environment where technology and assessment at a distance may encourage easy and innovative ways of cheating. The purpose of this quantitative study was to assess campus-based and online students’ attitudes and perceptions toward academic dishonesty. Data were collected via the Student Academic Honesty Survey to measure student perceptions of academic dishonesty to determine the following: (a) whether biological males and females differed in their perceptions of academic dishonesty, (b) the predictive relationships between perceptions of academic dishonesty and locus of control after controlling for type of school, and (c) …

Perceived Factors Of Intimate Partner Violence On Women Diagnosed With Post-Traumatic Stress Disorder, Angela M. Halcovich

Walden Dissertations and Doctoral Studies

Post-Traumatic Stress Disorder (PTSD) is a prevalent diagnosis, and many human and social services professionals strive to understand its components, to ensure that they serve the population properly. However, little is known about how PTSD may influence women’s vulnerabilities to and future experiences of intimate partner violence (IPV). Emphasizing relationship coaching, which provides tools to foster healthy relationships, within the therapeutic curricula on rehabilitation for women with PTSD may result in reduced chances to experience IPV as women integrate back into their everyday life after being diagnosed and treated for PTSD. The purpose of this generic qualitative study was to …

Effect Of Menstrual Cycle Phase On The Rewarding Properties Of Alcohol In Women, Annie K. Griffith

Theses and Dissertations--Psychology

Compared with men, women are disproportionately affected by alcohol, including greater risks of behavioral impairment and relapse. One likely mechanism underlying this disparity is fluctuations of ovarian hormones, particularly estradiol (E2), across phases of the menstrual cycle. Pre-clinical and clinical studies have shown that higher E2 levels correlate with heavier patterns of alcohol consumption, suggesting E2 may modulate drinking. This relationship is thought to be mediated by the rewarding properties of alcohol. The present thesis tested the hypothesis that elevated E2 during the late follicular phase would increase the rewarding properties of alcohol. Fifty young-adult women participated in a within-subjects …

The Effects Of Extended Fructose Access On Relative Value And Demand For Fructose, Saccharin, And Ventral Tegmental Stimulation, Megan Halloran

Theses and Dissertations--Psychology

Globally, food addiction (FA) is a growing area of research and is largely attributed to the availability of foods that are both energy dense and high in fats and sugars. Further, it has been suggested, that sugar and fat, when consumed frequently, have properties similar to drugs of abuse. While the validity of FA is questioned, researchers have drawn parallels between substance use disorder (SUD) and FA. For example, sugar binge models emphasize craving, withdrawal and binging as primary components of FA, which are also hallmarks of SUD. Additionally, both natural rewards, like sugars, and drug rewards act on the …

Calcium Imaging Of Central Amygdala Activity After Fentanyl Escalation, Samantha Malone

Theses and Dissertations--Psychology

Evidence suggests that rats given long access (LgA) sessions to self-administer (SA) opioids escalate their intake, while also showing greater withdrawal severity and drug-induced reinstatement compared to rats maintained on short access (ShA) daily SA sessions. Little is known about the neural changes that occur during opioid escalation that may impact withdrawal and relapse. Past work examining opioid SA using ShA sessions in rodents has identified the central amygdala (CeA) as an area of interest that becomes hyperactive in acute withdrawal and may be involved in the incubation of craving that occurs after protracted withdrawal. However, these studies have not …

Targeting The Subacute Progression Of Hippocampal Cellular Senescence Following Repetitive Mild Traumatic Brain Injury, Jacob Edward Exline

Master's Theses

Repetitive mild traumatic brain injury (rmTBI) increases an individual’s risk for developing persistent deficits in recognition memory with symptoms experienced by up to 30% of rmTBI patients. Cellular senescence has been suggested as an underlying mechanism of persistent rmTBI symptoms; however, the subacute progression of cellular senescence following rmTBI has not been evaluated. Furthermore, the use of subacute testosterone administration to treat persistent recognition memory deficits and the cellular and molecular underpinnings has yet to be well characterized. Our lab utilizes a 5-hit closed-head rmTBI rat model to induce deficits in recognition memory and determine the effects of subacute testosterone …