Neuroscience and Neurobiology Commons^™

Understanding The Role Of Lipids Derived From The Gut Microbes In A Mouse Model Of Obesity-Induced Peripheral Pain, Raiza Rafael-Bonomo Hardy

Dissertations

The increase in obesity has been accompanied by a rise in the prevalence of painful peripheral neuropathy. Recently, studies have suggested a role for gut microbiome in the development of some peripheral pain, including chemotherapy- induced pain and fibromyalgia. In the present dissertation, we showed that modulation of gut microbiome in obese mice alleviated neuropathic indices, concurrent with changes in immune cell profile within the peripheral nerve system. We demonstrated that fecal transplantation from lean to obese mice decreased obesity-induced pain and restored nerve density in the skin. These improvements were accompanied by changes in peripheral nerve system gene expression, …

Characterizing Galectin And Lysosomal Rupture's Role In Spreading Parkinson Disease Pathology, Kevin Burbidge

Dissertations

The misfolding and subsequent accumulation of alpha-synuclein (α-syn) is central to the pathogenesis of Parkinson's disease (PD). Several lines of evidence suggest pathological α-syn spread cell-to-cell via a "prion-like" mechanism. Furthermore, this pathological α-syn is capable of "seeding" further misfolding of non-pathological α-syn, converting them to the pathological form. While a vast body of both genetic and experimental evidence indicates that α-syn is critical to PD development, how α-syn induces progressive neuronal dysfunction and cell death remains unclear.Autophagy, conventional for macroautophagy, is the primary degradation pathway for α-syn aggregates. Autophagy also influences the unconventional secretion of both pathological and non-pathological …

Mathematical Models And Tools To Understand Coupled Circadian Oscillations And Limit Cycling Systems, Guangyuan Liao

Dissertations

The circadian rhythm refers to an internal body process that regulates many body processes including the sleep-wake cycle, digestion and hormone release. The ability of a circadian system to entrain to the 24-hour light-dark cycle is one of the most important properties. There are several scenarios in which circadian oscillators do not directly receive light-dark forcing. Instead they are part of hierarchical systems in which, as \peripheral" oscillators, they are periodically forced by other \central" circadian oscillators that do directly receive light input. Such dynamics are modeled as hierarchical coupled limit cycle systems. Those models usually have a large population, …

Investigating The Combined Effects Of Whole Body Vibration And Vestibular Stimulation On Spasticity And Dystonia In Cerebral Palsy, Peter A. Michael

Dissertations

This study identifies and addresses three voids and potential shortcomings associated with the classification, assessment and management of Cerebral Palsy (CP). These concerns should not undermine the significant advancement that has been made in this specific branch of rehabilitation, but addressing them is necessary. Cerebral Palsy is a group of motor impairments due to hypoxic-ischemic brain damage around the time of birth and very commonly manifests as excessive muscle tone and poor motor control. There are classifications within CP including spasticity and dystonia.

First, a level of discrepancy is present in the classification of CP between the clinical and research …

Microglia Induced Neuroinflammation Through The Nlrp3 Inflammasome Following Blast Traumatic Brain Injury, Daniel Younger

Dissertations

The incidence of traumatic brain injury (TBI) among military personnel have been steadily increasing with modern conflicts. A recent RAND report estimated 320,000 service members, totaling 20% of deployed forces, suffer from TBI. However, of this population roughly 60% have not seen a medical professional specifically for TBI. Unlike the civilian population, the primary cause of TBI for active-duty military personnel is blast exposure. Blasts now account for over 70% of all US military casualties in operation Iraqi Freedom (OIF) and Operation enduring freedom (OEF) and are the major cause of TBI. Among many pathological mechanisms associated with blast TBI, …

Modulation Of Cerebellar Purkinje Cell Activity With Low Intensity Electric And Ultrasound Stimulation, Ahmet S. Asan

Dissertations

Non-invasive brain stimulation (NIBS) techniques garner significant interest due to their potential to offer instantaneous and region-specific treatments to neurological disorders. The cerebellum is one of the target sites for NIBS methods due to its central role in motor and cognitive functions. Among several modulation techniques, transcranial electric stimulations (tEs), in particular, transcranial direct and alternating current stimulations (tDCs/tACs), and low intensity focused ultrasound stimulation (LIFUS) show encouraging outcomes in clinical applications. tDCs and tACs are favored due to their low cost and accessibility while LIFUS offers high spatial resolution and deeper penetration without affecting the surrounding structures. In order …

Data Assimilation For Conductance-Based Neuronal Models, Matthew Moye

Dissertations

This dissertation illustrates the use of data assimilation algorithms to estimate unobserved variables and unknown parameters of conductance-based neuronal models. Modern data assimilation (DA) techniques are widely used in climate science and weather prediction, but have only recently begun to be applied in neuroscience. The two main classes of DA techniques are sequential methods and variational methods. Throughout this work, twin experiments, where the data is synthetically generated from output of the model, are used to validate use of these techniques for conductance-based models observing only the voltage trace. In Chapter 1, these techniques are described in detail and the …

The Roles Of Inhibition In C. Elegans Locomotion, Lan Deng

Dissertations

Inhibition plays important roles in modulating neural activities at different levels from small synapses to brain regions, and different systems from sensory to motor. To achieve translocation, locomotor systems produce alternation of antagonist muscles, including axial posture and limb movement and alternation. In the nematode C. elegans, a cross-inhibition circuit, involving excitatory cholinergic and inhibitory GABAergic motoneurons, is believed to generate the dorsoventral alternation of body-wall muscles that supports backward undulatory locomotion. This dissertation challenges this prevalent hypothesis, delves into studying different roles of inhibition, and depicts the expression pattern and functional role of ionotropic GABAA receptor, UNC-49, in motoneurons …

Schwann Cells In Combination With Gag-Mimetic Scaffolds For Spinal Cord Repair, Sharareh Hashemi

Dissertations

Spinal cord injury (SCI) being a devastating neurological dysfunction can cause extensive irreversible neuronal loss and axonal damage. Fifty-four cases of spinal cord injury per million people occur annually in the United States. Due to the loss of glial cells and demyelination of axons, the neuronal function of surviving neurons is disrupted leading to permanent loss of sensory and motor functions. The glial scar formed by astrogliosis at the chronic stage protects undamaged tissues, but it is known to be a major barrier for axonal regeneration. The limited regeneration capacity of spinal cord makes it challenging to successfully treat the …

Sedative And Neurotoxic Properties Of Brexanolone Compared To Midazolam In The Developing Rodent Brain, Jacob Huffman

Dissertations

The developing brain is susceptible to extensive neurotoxicity following exposure to sedative/anesthetic drugs (SADs). Every year hundreds of thousands of children around the world are exposed to SADs with no viable non-neurotoxic agents approved for clinical use. Allopregnanolone (AlloP) has well-established sedative effects in adults and neonates. AlloP and many SADs produce sedation/anesthesia through allosteric modulation of GABA_A receptors, which is one of two principal mechanisms behind SAD-induced neurotoxicity. Evidence suggests AlloP has the unique capacity to regulate key apoptotic factors in adults and is widely involved with critical stages of neurodevelopment, indicating this neurosteroid might serve as a …

Perivascular Waste Metabolites Clearance In Central Nervous System (Cns), Yiming Cheng

Dissertations

Efficient clearance of interstitial waste metabolites is essential for normal brain homeostasis. Such effective clearance is hampered by the lack of a lymphatic system in the brain, and the cerebrospinal fluid (CSF) is unable to clear large size waste metabolites in the brain. Here, a novel idea that brain arterial endothelium and smooth muscle cells reactivity regulates the clearance of these water-insoluble large size waste metabolites through the perivascular dynamic exchange, and that low dose ethanol promotes this perivascular clearance is proposed.

In Aim 1, the biodistribution of a large size waste metabolite (Amyloid-β protein mimic) in rat perivascular space …

Cerebro-Vascular Disruption Mediated Initiation And Propagation Of Traumatic Brain Injury In A Fluid Percussion Injury Model, Xiaotang Ma

Dissertations

Traumatic brain injury (TBI) is a major health problem for over 3.17 million people in the US. There is no FDA-approved drug for the treatment because the injury mechanisms have not been clearly identified. The knowledge gap is addressed here by the lateral fluid percussion injury (FPI) rat model, through the understanding of layer-structured mechanisms from physical vascular rupture to acute necrosis, as well as biochemical changes in perivascular space as secondary events.

Firstly, the cerebrovascular hemorrhage and related infarct volume are investigated as the primary events in moderate FPI, which is found to be increased with injury severity in …

A Computational Study Of Sleep And The Hemispheres Of The Brain, Tera Ashley Glaze

Dissertations

Sleep and sleep cycles have been studied for over a century, and scientists have worked on modeling sleep for nearly as long as computers have existed. Despite this extensive study, sleep still holds many mysteries. Larger and more extensive sleep-wake models have been developed, and the circadian drive has been depicted in numerous fashions, as well as incorporated into scores of studies. With the ever-growing knowledge of sleep comes the need to find more ways to examine, quantify, and define it in the context of the most complex part of the human anatomy – the brain. Presented here is the …

Developmental And Sex Modulated Neurological Alterations In Autism Spectrum Disorder, Azeezat Azeez

Dissertations

Autism Spectrum Disorder (ASD) was first described in 1943 by Dr. Leo Kranner in a case study published in The Nervous Child. It is a neurodevelopment disorder, with a range of clinical symptoms. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), used by clinicians to diagnose mental disorders, a child needs to have persistent social deficits, language impairments, and repetitive behaviors, that cannot be explained by neurological damage or intellectual disability. It is known that children diagnosed with ASD are often are developmentally delayed therefore alterations in the typical developmental trajectory should be a major factor in …

Redefining Burnout: Exploring Common Conceptualizations And The Neurophysiology Of Chronic Stress To Establish An Integrated Allostatic Model, Danny A. Guzzi

Dissertations

Burnout is a widely researched stress-related phenomenon associated with numerous adverse outcomes for employees and organizations. Unfortunately, burnout is not well understood and research to this point has been flawed due to a lack of consensus on the definition, dimensionality, and context of the construct. Prevalent conceptualizations of burnout have been criticized for being arbitrarily developed without solid theoretical foundation and for failing to clearly distinguish burnout from depression or other work-related conditions such as compassion fatigue, secondary traumatization, and vicarious traumatization. The current project first examines relevant literature to identify commonalities among prevalent burnout conceptualizations. Then relevant stress research …

Confabulation In Individuals With Disorders Of The Corpus Callosum: Educational Implications, Cheryl Lynn Wright

Dissertations

Individuals with disorders of the corpus callosum (DCC) may have subtle cognitive differences. Historically, confabulation has been associated with DCC. Therapies to mitigate confabulation is a newly emerging field. This study explores the possible educational implications that those with DCC may experience with confabulation.

The community of people with DCC and the community of people who interact with individuals with DCC were surveyed to ascertain the prevalence of confabulation within the population of those with DCC. A subset of questions probed whether age and/or gender impact the rates of reported confabulation. The research paradigm included a section that covered the …

Evolution Of Caffeine Biosynthetic Enzymes And Pathways In Flowering Plants, Ruiqi Huang

Dissertations

Convergent evolution generally refers to the independent evolution of similar biological function more than once in unrelated species. Caffeine is thought to have evolved by convergence, and is naturally produced through secondary metabolism in plants to defend against pathogen attack and insect feeding or to attract pollinators. The same caffeine biosynthetic pathway has been elucidated in Camellia (tea) and Coffea (coffee), in which xanthosine is sequentially methylated to caffeine via 7-methylxanthine and theobromine. However, although the same catalysis pathway is used, different (paralogous) enzymes in the SAMT/BAMT/theobromine synthase (SABATH) multigene family are used in the two species. In my dissertation, …

Elucidating Mechanisms Of Protein Aggregation In Alzheimer’S Disease Using Antibody-Based Strategies., Benjamin A. Colvin

Dissertations

Alzheimer’s Disease (AD) is a devastating neurodegenerative disorder. There are two characteristic histopathological hallmarks in the brain: senile plaques and neurofibrillary tangles, composed of insoluble aggregates of the amyloids Amyloid-β (Aβ) and tau protein, respectively. These diagnostic markers, though distinctive, are not apparent effectors of AD pathology. Evidence has mounted suggesting smaller soluble aggregates (oligomers) of Aβ or tau are the true drivers of disease progression. This dissertation presents several amyloid biophysics projects. Aggregate biophysical parameters such as weight, shape, and conformation were measured using a range of methodologies, including Multiangle Light Scattering, Dynamic Light Scattering, UV-Circular Dichroism, UV-Fluorescence, Scanning …

A Novel Role For Osteopontin In Facilitating West Nile Virus Neuroinvasion, Amber M. Paul

Dissertations

West Nile virus (WNV) is a positive-sensed, single-stranded RNA flavivirus that can cause human neuroinvasive diseases, including encephalitis, meningitis, and flaccid paralysis. The mechanisms by which WNV enters the central nervous system and the host-factors that are involved in WNV-neuroinvasiveness are not completely understood. Osteopontin (OPN), a multifunctional glycoprotein, has been implicated as a bio-marker for a number of neuroinflammatory diseases. In particular, secreted (s)OPN has been implicated to participate in recruitment of polymorphonuclear neutrophils (PMN) to sites of its expression, while PMNs have been suggested to act as WNV reservoirs. Therefore, sOPN recruitment of PMNs may contribute to neuroinvasive …

Anxiety-Like Behaviors And C-Fos Expression In Adult Zebrafish: Effects Of Housing Conditions, Alcohol And Caffeine, Adam Douglas Collier

Dissertations

Alcohol abuse is the third largest risk factor for disease world, responsible for an estimated 3.3 million deaths each year. The concomitant ingestion of alcohol and caffeine is hypothesized to increase risk factors associated with alcohol use alone by reducing subjective effects of intoxication. The zebrafish (Danio rerio) has recently garnered attention from researchers as an effective pre-clinical in-vivo animal model in behavioral pharmacology research, largely due to small size, low-cost and ease of drug delivery. A number of studies have reported the effects of alcohol and caffeine on zebrafish behavior at a variety of doses. However, the …

Endocytic Vesicle Rupture In The Pathogenesis And Propagation Of Neurodegenerative Proteinopathies, William P. Flavin

Dissertations

Numerous pathological amyloid proteins spread from cell-to-cell during neurodegenerative disease, facilitating the propagation of cellular pathology and disease progression. Understanding the mechanism by which disease-associated amyloid protein assemblies enter target cells and induce cellular dysfunction is therefore key to understanding the progressive nature of such neurodegenerative proteinopathies. In this study, we utilized an imaging-based assay to monitor the ability of disease-associated amyloid assemblies to induce the rupture of intracellular vesicles following endocytosis, as well as to elucidate the cellular consequences of this damaging mechanism of invasion. We observed that the ability to induce vesicle rupture is a conserved feature of …

The Effects Of Alcohol And Traumatic Brain Injury On Neural Stem Cell Responses, Son Trung Ton

Dissertations

Traumatic brain injury (TBI) is a major source of disability in modern societies. However, there are no good pharmacological strategies for treating long-term TBI complications because we do not fully understand the injury processes that occur afterward. Moreover, a significant percent of patients entering the emergency room with TBI have a blood alcohol level above the legal limit. Alcohol use and intoxication is a widespread issue in our society. Binge drinking is the most common way in which alcohol is consumed, and alarmingly, Americans of all age groups binge drink on a frequent basis. Despite the prevalence of alcohol intoxication …

Sex Differences In Stroke Recovery: Synaptic Proteins And The Growth Inhibitory Protein Nogo A, Vincent Joseph Borkowski

Dissertations

Ischemic stroke is a major world-wide health problem, resulting in death and disability especially in the older population. A sex difference exists in functional recovery post-stroke, with post-menopausal women having worse functional outcome as compared to age-matched men. Although the mechanisms underlying this sex difference are not entirely clear, it is recommended that any potential therapy for stroke recovery be tested in pre-clinical models including both male and females in order to determine the efficacy of the proposed treatment on the entire population. We have reported a novel therapy to enhance brain plasticity and improve functional recovery after stroke in …

Regulation Of Glial Cell Line-Derived Neurotrophic Factor (Gdnf) Production In Voluntary And Involuntary Muscle, John-Mary Vianney

Dissertations

Glia cell line-derived neurotrophic factor (GDNF) is a survival factor for subpopulations of neurons, including somatic and autonomic motor neurons. These neurons depend, in part, on GDNF that is synthesized and secreted by their target tissues. It has been shown that a number of tissues in the periphery express GDNF and these target tissues differ in their composition, function, and in the case of different muscle cell types, their contractile characteristics. Whether the processes regulating GDNF production in these different tissues is similar or different is poorly understood. The broad goal of this study is to examine factors that normally …

The Molecular Components Of Estrogen Receptor Beta (Erβ) Signaling In Neuronal Sytems, Natasha Mott

Dissertations

With increasing life expectancy, women are now living upwards of 50 years without circulating estrogens, therefore, it is essential to investigate how the brain is changed by estrogen deprivation and also how aging influences these changes. The Women's Health Initiative (WHI) study spurred rigorous debate regarding estrogen therapy for postmenopausal women due to dichotomous effects of estrogens in menopausal and post-menopausal women. Meta-analyses of the WHI study revealed that after circulating estrogens are depleted for many years re-exposure may cause aberrant, negative health effects, indicating that there is an age-related `switch' in estrogen signaling around menopause. These age-related effects of …

Exercise Alters Glial Cell Line-Derived Neurotrophic Factor (Gdnf) Protein Content In The Spinal Cord, Monica Janine Mccullough

Dissertations

Neurotrophic factors may play a role in exercise-induced neuroprotective effects; however, it is not known if exercise mediates changes in glial cell line-derived neurotrophic factor (GDNF) protein levels in the spinal cord. The aim of the studies described herein was to determine if exercise alters GDNF protein expression in the lumbar spinal cord of healthy and diseased animals. The lumbar spinal cord was analyzed from adult rats aged 6-, 12-, 18- and 24-months, and from transgenic amyotrophic lateral sclerosis (ALS) mice and wild-type mice aged 3 months. Animals had undergone either forced wheel running, voluntary wheel running or swimming for …

Molecular Expression Of Neuroprotective And Neurodestructive Signaling Systems Following Axotomy-Induced Target Disconnection: Relevance To Als, Melissa Marie Haulcomb

Dissertations

Amyotrophic Lateral Sclerosis (ALS) is the most common adult motoneuron (MN) degenerative disease. Discovery of a portion of familial cases with a mutation in the gene superoxide dismutase 1 (SOD1) gene led to the development of a transgenic mouse model. Pre-symptomatic SOD1 mice show no symptoms well into adulthood, however once symptom onset has occurred they display pathological hallmarks of ALS. The initial pathological event is loss of neuromuscular junctions in the lower limbs and therefore the die-back theory of ALS, suggests disconnection from the target musculature leads to MN degeneration. Our lab utilizes a peripheral nerve injury model to …

Neuroendocrine Consequences Of Binge Alcohol Exposure During Peri-Puberty On Functioning Of The Hypothalamo-Pituitary-Adrenal (Hpa) Axis, Magdalena Malgorzata Przybycien-Szymanska

Dissertations

Binge alcohol (EtOH) exposure in adolescence is a fundamental health concern. In 2005, over 20% of teenagers between ages 15 and 17 reported binge drinking behavior within a one month period preceding the survey (Dept. of Health and Human Services: Substance Abuse and Mental Health Services Administration). Binge drinking is defined as consuming enough alcohol within a 2.0 h period to bring blood alcohol concentration above 0.08%. In the adolescent population, this type of alcohol exposure tends to be repeated. In adults, alcohol abuse has been correlated with increased incidence of mood disorders and these disorders are characterized by dysregulation …

The Role Of Sdf1/Cxcr4 Signaling In Opioid-Induced Hypernociception, Natalie Wilson

Dissertations

Opioids currently represent the best treatment option for severe and chronic pain conditions. Opioids while effective at controlling pain states also come with a number of side effects such as respiratory depression, urinary retention, dependence, tolerance, and opioid-induced hypernociception (OIH). OIH is a phenomenon in which opioids induce pain and this pain is often experienced at a site separate from the site of injury. Much research has been conducted investigating the mechanism of OIH, but the mechanism remains unsolved. One potential mechanism that has yet to be adequately explored is chemokines. Chemokines role in OIH is warranted given recent studies …

The Role Of Nogo-A In Memory And Neuronal Plasticity In The Aged Rodent Brain, Rebecca Lynn Gillani

Dissertations

The long-term effects of stroke often include cognitive impairments, but other than cognitive rehabilitation, which is often not fully successful, there is no intervention to treat cognitive impairments in stroke survivors. Our laboratory has previously shown that immunotherapy directed against the Nogo-A protein, which is enriched on oligodendrocytes, improves recovery of skilled forelimb sensorimotor function in adult and aged rats after an ischemic stroke lesion to the sensorimotor cortex. Furthermore, this recovery was correlated with axonal sprouting from intact pathways to denervated areas, as well as dendritic sprouting and increased dendritic spine density in the contralateral sensorimotor cortex. In the …