Medical Neurobiology Commons^™

Gene Expression And Alzheimer's Disease: Evaluation Of Gene Expression Patterns In Brain And Blood For An Alzheimer's Disease Mouse Model, Amanda Hazy

Senior Honors Theses

Previous studies have established a causative role for altered gene expression in development of Alzheimer’s disease (AD). These changes can be affected by methylation and miRNA regulation. In this study, expression of miRNA known to change methylation status in AD was assessed by qPCR. Genome-wide expression changes were determined by RNA-sequencing of mRNA from hippocampus and blood of control and AD mice. The qPCR data showed significantly increased expression of Mir 17 in AD, and sequencing data revealed 230 genes in hippocampus, 58 genes in blood, and 8 overlapping genes showing significant differential expression (p value ≤ 0.05). Expression data …

Mitochondrial And Neuroprotective Effects Of Phenelzine Related To Scavenging Of Neurotoxic Lipid Peroxidation Products, John Cebak

Theses and Dissertations--Neuroscience

Lipid peroxidation is a key contributor to the pathophysiology of traumatic brain injury (TBI). Traditional antioxidant therapies are intended to scavenge the free radicals responsible for either the initiation or propagation of lipid peroxidation (LP). However, targeting free radicals after TBI is difficult as they rapidly react with other cellular macromolecules, and thus has a limited post-injury time window in which they may be intercepted by a radical scavenging agent. In contrast, our laboratory has begun testing an antioxidant approach that scavenges the final stages of LP i.e. formation of carbonyl-containing breakdown products. By scavenging breakdown products such as the …

Targeting Methylglyoxal And Ppar Gamma To Alleviate Neuropathic Pain Associated With Type 2 Diabetes, Ryan B. Griggs

Theses and Dissertations--Physiology

Neuropathic pain affects up to 50% of the 29 million diabetic patients in the United States. Neuropathic pain in diabetes manifests as a disease of the peripheral and central nervous systems. The prevalence of type 2 diabetes is far greater than type 1 (90%), yet the overwhelming focus on type 1 models this has left the mechanisms of pain in type 2 diabetes largely unknown. Therefore I aimed to improve the current mechanistic understanding of pain associated with type 2 diabetes using two preclinical rodent models: Zucker Diabetic Fatty rats and db/db mice. In addition, I highlight the translational importance …

Accommodating Hyperaroused Information Processing In Persons At Risk For Alcoholism, Kellianne Clark, Jaclyn Cutler

Student Scholar Symposium Abstracts and Posters

In the search for the factors related to the heightened alcoholism risk in adult children of alcoholics (ACOA), it has been reported that these persons possess a high incidence of attention deficit disorders (ADD) as determined by clinical assessment instruments. However, investigations of alcoholism risk and ADD indicate that, in contrast to the hypoarousal model of ADD, the ACOA’s attention problems represent hyperarousal of attention mechanisms resulting in reduced ability to select and encode relevant information. If true, then unlike persons with ADD, clinical and cognitive assessments of ACOAs would benefit if the ACOA was provided with more time to …

Postural Sway And Brain Hemispheric Power Spectral Density Under Different Attentional Focus Conditions, Sharon Jalene

UNLV Theses, Dissertations, Professional Papers, and Capstones

The purpose of this study was to determine the differences, if any, in the root mean square error (RMSE) of postural sway and hemispheric power spectral density (PSD) in the alpha and beta bands (8-12Hz and 12-25Hz) during different conditions of attentional focus (i.e., internal focus (IF), and external focus (EF) and a control condition (C)). Previous studies have shown that the adoption of IF and EF significantly alter motor performance and that EF promotes automaticity (Wulf, 2013). Sports performance and balance studies utilizing EEG spectral analyses report increased alpha oscillations during expert performance and stable balance and increased beta …

Hemispheric Asymmetry In The Perception Of Musical Pitch Structure, Matthew Adam Rosenthal

UNLV Theses, Dissertations, Professional Papers, and Capstones

Both the left and right hemispheres contribute to the perception of pitch structure

in music. Music researchers have attempted to explain the observed asymmetries in the perception of musical pitch structure by characterizing the dominant processing style of each hemisphere. However, no existing characterizations have been able to account for all of the empirical findings. To better explain existing empirical findings, this dissertation characterizes the left hemisphere as dominant in temporal pitch processing (i.e. with respect to the sequential ordering of pitches) and the right hemisphere as dominant in non-temporal pitch processing (i.e. without respect to the sequential ordering of …

The Effect Of Spinal Cord Injury On Vagal Afferents., April N. Herrity

Electronic Theses and Dissertations

Spinal cord injury (SCI) is a significant public health concern that leaves patients with a multitude of life-long disabilities. Major complications of SCI apart from paralysis, include deficits in bladder and bowel function. Lower urinary tract dysfunction continues to remain a top priority issue affecting quality of life for this population. The majority of visceral organs receive a dual sensory innervation from both spinal nerves as well as the vagus nerve. Following SCI, the vagus nerve is a potential pathway through which information from regions below the level of a spinal injury can travel directly to the brainstem, bypassing the …

A Pilot Study Of Basal Ganglia And Thalamus Structure By High Dimensional Mapping In Children With Tourette Syndrome, Alton C. Williams, Marie E. Mcneely, Deanna J. Greene, Jessica A. Church, Stacie L. Warren, Johanna M. Hartlein, Bradley L. Schlaggar, Kevin J. Black, Lei Wang

Kevin J. Black, MD

No abstract provided.

Analysis Of Differential Mrna And Mirna Expression In An Alzheimer’S Disease Mouse Model, Amanda Hazy, Matthew Dalton

Other Undergraduate Scholarship

Research has shown that changes in gene expression play a critical role in the development of Alzheimer’s Disease (AD). Our project will evaluate genome-wide RNA expression patterns from brain and blood in an AD mouse model. This analysis will provide insight regarding the mechanisms of AD pathology as well as determine a possible diagnostic tool utilizing RNA expression patterns found in the blood as biomarkers for AD.

Swimming Against The Tide: Investigations Of The C-Bouton Synapse, Adam S. Deardorff, Shannon H. Romer, Patrick M. Sonner, Robert E. W. Fyffe

Neuroscience, Cell Biology & Physiology Faculty Publications

C-boutons are important cholinergic modulatory loci for state-dependent alterations in motoneuron firing rate. m2 receptors are concentrated postsynaptic to C-boutons, and m2 receptor activation increases motoneuron excitability by reducing the action potential afterhyperpolarization. Here, using an intensive review of the current literature as well as data from our laboratory, we illustrate that C-bouton postsynaptic sites comprise a unique structural/functional domain containing appropriate cellular machinery (a “signaling ensemble”) for cholinergic regulation of outward K⁺ currents. Moreover, synaptic reorganization at these critical sites has been observed in a variety of pathologic states. Yet despite recent advances, there are still great challenges …

Effects Of Pde4 Pathway Inhibition In Rat Experimental Stroke, Fan Yang, Rachita K. Sumbria, Dong Xue, Chuanhui Yu, Dan He, Shuo Liu, Annlia Paganini-Hill, Mark J. Fisher

Pharmacy Faculty Articles and Research

PURPOSE: The first genomewide association study indicated that variations in the phosphodiesterase 4D (PDE4D) gene confer risk for ischemic stroke. However, inconsistencies among the studies designed to replicate the findings indicated the need for further investigation to elucidate the role of the PDE4 pathway in stroke pathogenesis. Hence, we studied the effect of global inhibition of the PDE4 pathway in two rat experimental stroke models, using the PDE4 inhibitor rolipram. Further, the specific role of the PDE4D isoform in ischemic stroke pathogenesis was studied using PDE4D knockout rats in experimental stroke. METHODS: Rats were subjected to either the …

Multiple Myeloma And Its Treatment Alter Peripheral Nervous System Structure And Function, Alyssa K. Kosturakis

Dissertations & Theses (Open Access)

MULTIPLE MYELOMA AND ITS TREATMENT ALTER PERIPHERAL NERVOUS SYSTEM STRUCTURE AND FUNCTION

Alyssa Katarina Kosturakis, BA

Supervisory Professor: Patrick M. Dougherty, PhD

Peripheral neuropathy is among the most deleterious side effects of frontline chemotherapeutics used to treat prevalent cancers. Chemotherapy-induced peripheral neuropathy (CIPN) refers to the collection of symptoms (e.g. pain, paresthesias and dysesthesias) that develop in distal, glabrous (non-hairy) skin of 20 to 100% of patients treated with chemotherapy. Peripheral neuropathy negatively impacts quality of life in cancer patients and survivors, is refractory to treatment, and is the impetus for dose-reduction and/or cessation of chemotherapy, thereby limiting treatment. Proteasome …

The Effect Of Acute Lps-Induced Immune Activation And Brain Insulin Signaling Disruption In A Diabetic Model Of Alzheimer's Disease, Andrew Scott Murtishaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer's disease (AD) is a neurodegenerative disorder marked by progressive cognitive impairments and pathological hallmarks that include amyloid plaques, neurofibrillary tangles, and neuronal loss. Several well-known mutations exist that lead to early-onset familial AD (fAD). However, these cases only account for a small percentage of total AD cases. The vast majority of AD cases are sporadic in origin (sAD) and are less clearly influenced by a single mutation but rather some combination of genetic and environmental risk.

The etiology of sAD remains unclear but numerous risk factors have been identified that increase the chance of developing AD. Among these risk …

Craniodental Anatomy Of A New Late Cretaceous Multituberculate Mammal From Udan Sayr, Mongolia., Amir Subhash Sheth

Electronic Theses and Dissertations

Multituberculates were the longest-lived group of early mammals, with a nearly worldwide distribution, and a temporal range from the Middle Jurassic to the Late Eocene. Multituberculates are typically represented by isolated teeth and jaw fragments; however, several localities in Mongolia revealed abundant, well-preserved multituberculate skulls and partial skeletons from the Late Cretaceous. This study is centered on two specimens of a new multituberculate taxon from a locality in the Gobi desert, Udan Sayr. Included is a (1) bone-by-bone description of the cranial and mandibular elements, as well as the dental features of both specimens, PSS-MAE 141 (holotype) and PSS-MAE 142, …

Effects Of Passive Immobilization On Locomotor Recovery After Spinal Cord Injury In Adult Rats., Kelsey Lee Stipp

Electronic Theses and Dissertations

Background: Spontaneous locomotor recovery in spinal rats has been attributed to animals moving freely in-cage. Environmental enrichment has been shown to increase in-cage movement and functional recovery subsequently. Anxiety has been shown to decrease overnight activity in rats. Methods: Rats were double-housed in medium cages (MC) or single-housed in tiny sized cages (TC). Slotted dividers allowed for partial isolation in TC. Overnight activity was monitored bi-weekly. The open field test and BBB’s were taken weekly. Gait analysis was performed at weeks six and eight. Results: MC showed higher overnight activity and improved gait overtime. No differences were found in BBB …

Frontal White Matter Integrity In Adults With Down Syndrome With And Without Dementia, David K. Powell, Allison Caban-Holt, Greg A. Jicha, William C. Robertson, Roberta Davis, Brian T. Gold, Frederick A. Schmitt, Elizabeth Head

Magnetic Resonance Imaging and Spectroscopy Center Faculty Publications

Adults with Down syndrome (DS) are at high risk for developing Alzheimer's disease after the age of 40 years. To detect white matter (WM) changes in the brain linked to dementia, fractional anisotropy (FA) from diffusion tensor imaging was used. We hypothesized that adults with DS without dementia (DS n = 10), DS with dementia (DSAD n = 10) and age matched non-DS subjects (CTL n = 10) would show differential levels of FA and an association with scores from the Brief Praxis Test and the Severe Impairment Battery. WM integrity differences in DS compared with CTL were found predominantly …

Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the …

Motor Axon Synapses On Renshaw Cells Contain Higher Levels Of Aspartate Than Glutamate, Dannette Shanon Richards, Ronald W. Griffith, Shannon H. Romer, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Motoneuron synapses on spinal cord interneurons known as Renshaw cells activate nicotinic, AMPA and NMDA receptors consistent with co-release of acetylcholine and excitatory amino acids (EAA). However, whether these synapses express vesicular glutamate transporters (VGLUTs) capable of accumulating glutamate into synaptic vesicles is controversial. An alternative possibility is that these synapses release other EAAs, like aspartate, not dependent on VGLUTs. To clarify the exact EAA concentrated at motor axon synapses we performed a quantitative postembedding colloidal gold immunoelectron analysis for aspartate and glutamate on motor axon synapses (identified by immunoreactivity to the vesicular acetylcholine transporter; VAChT) contacting calbindin-immunoreactive (-IR) Renshaw …

Antioxidant Gene Therapy Against Neuronal Cell Death, Juliana Navarro-Yepes, Laura Zavala-Flores, Anandhan Annadurai, Fang Wang, Maciej Skotak, Namas Chandra, Ming Li, Aglaia Pappa, Daniel Martinez-Fong, Luz Maria Del Razo, Betzabet Quintanilla-Vega, Rodrigo Franco

Department of Psychology: Faculty Publications

Oxidative stress is a common hallmark of neuronal cell death associated with neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, as well as brain stroke/ischemia and traumatic brain injury. Increased accumulation of reactive species of both oxygen (ROS) and nitrogen (RNS) has been implicated inmitochondrial dysfunction, energy impairment, alterations in metal homeostasis and accumulation of aggregated proteins observed in neurodegenerative disorders, which lead to the activation/modulation of cell death mechanisms that include apoptotic, necrotic and autophagic pathways. Thus, the design of novel antioxidant strategies to selectively target oxidative stress and redox imbalance might represent important therapeutic approaches against neurological disorders. …

Adenosine Production Is Essential For Closing The Critical Period Of Cortical Plasticity, Rachel A. Chassan

Theses and Dissertations (ETD)

Sensory inputs from the external world are represented as highly organized systems in the adult brain for effective adaptation to the environment. At the cortical level, this organization is referred to as cortical maps. The establishment of cortical maps begins with early life experiences during the critical period, a brief period during development of heightened sensitivity to sensory stimuli. During this time, organization of cortical maps is plastic and highly subject to change through passive sensory experience. As an animal matures, the critical period closes and changes to cortical maps occur less freely. The cellular mechanisms of cortical map plasticity …