Medical Neurobiology Commons^™

Current State Of Preeclampsia Mouse Models: Approaches, Relevance, And Standardization, Christopher A. Waker, Melissa R. Kaufman, Thomas L. Brown

Neuroscience, Cell Biology & Physiology Faculty Publications

Preeclampsia (PE) is a multisystemic, pregnancy-specific disorder and a leading cause of maternal and fetal death. PE is also associated with an increased risk for chronic morbidities later in life for mother and offspring. Abnormal placentation or placental function has been well-established as central to the genesis of PE; yet much remains to be determined about the factors involved in the development of this condition. Despite decades of investigation and many clinical trials, the only definitive treatment is parturition. To better understand the condition and identify potential targets preclinically, many approaches to simulate PE in mice have been developed and …

Poster: Sars-Cov-2 Neuroinvasion, Heather M. Tatusko

Nursing Student Class Projects (Formerly MSN)

Over the last century, science and literature has reported neurological manifestations during various disease outbreaks as well as long-term sequelae following epidemics and pandemics. Some of the first neurological symptoms reported with Coronavirus Disease 2019 (COVID-19; caused by severe acute respiratory syndrome coronavirus 2 [SARS-Cov-2]) were anosmia and dysgeusia, suggesting SARS-CoV-2 penetrance of the central nervous system (CNS). To date, the definite clinical and pathological basis of CNS involvement of SARS-CoV-2 remains poorly understood, with the neurovirulence of SARS-CoV-2 and its neuroinvasive potential remaining largely unknown. The author’s poster will explore neurological manifestations of COVID-19 disease, the direct and indirect …

Effects Of Genetics And Sex On Hippocampal Gene Expression And Adolescent Behaviors Following Neonatal Ethanol Exposure In Bxd Recombinant Inbred Mice, Jessica A. Baker

Theses and Dissertations (ETD)

Fetal alcohol spectrum disorders (FASD) are the leading preventable neurodevelopmental disorders in the western world. A hallmark symptom of FASD is cognitive and learning deficits that present in early childhood and continue throughout adulthood. Teratogenic effects of alcohol include increased cell death in the hippocampus, a brain region critically important in learning and memory. Genetics have been shown to have a role in the severity of alcohol’s teratogenic effect on the developing brain. Previous work in our lab identified differential vulnerability to ethanol-induced call death in the hippocampus using fourteen BXD strains and the two parental strains. The goal of …

Astrocyte-Derived Thrombospondin Induces Cortical Synaptogenesis In A Sex-Specific Manner, Anna Mazur, Ean H. Bills, Kayla M. Deschepper, James C. Williams, Brandon J. Henderson, W. Christopher Risher

Biomedical Sciences

The regulation of synaptic connectivity in the brain is vital to proper functioning and development of the CNS. Formation of neural networks in the CNS has been shown to be heavily influenced by astrocytes, which secrete factors, including thrombospondin (TSP) family proteins, that promote synaptogenesis. However, whether this process is different between males and females has not been thoroughly investigated. In this study, we found that cortical neurons purified from newborn male rats showed a significantly more robust synaptogenic response compared with female-derived cells when exposed to factors secreted from astrocytes. This difference was driven largely by the neuronal response …

Taste Learning In Insular Cortex: Plasticity Is Influenced By Experience Type, Stephanie Marie Staszko

Theses and Dissertations (ETD)

The gustatory cortex (GC) has long been studied as the main cortical area encoding taste stimuli and likely integrates sensory, visceral, and emotional information to guide taste-related behaviors. However, our understanding of cortical taste coding on a single-cell level has only become clear in recent years. The anatomical location of GC on the lateral and ventral surface of the brain makes it difficult to target with traditional imaging methods. Thus, much of what we know about cortical taste coding and cortical taste plasticity has been derived either from multiunit electrode recordings or anesthetized imaging experiments, techniques which lack the ability …

The Role Of Action Potential Waveform In Failure Of Excitation Contraction Coupling, Xueyong Wang, Murad Nawaz, Steve R.A. Burke, Roger Bannister, Brent D. Foy, Andrew A. Voss, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Excitation contraction coupling (ECC) is the process by which electrical excitation of muscle is converted into force generation. Depolarization of skeletal muscle resting potential contributes to failure of ECC in diseases such as periodic paralysis, ICU acquired weakness and possibly fatigue of muscle during vigorous exercise. When extracellular K+ is raised to depolarize the resting potential, failure of ECC occurs suddenly, over a range of several mV of resting potential. While some studies have hypothesized the sudden failure of ECC is due to all-or-none failure of excitation, other studies suggest failure of excitation is graded. Intracellular recordings of action potentials …

Immunological And Hematological Outcomes Following Protracted Low Dose/Low Dose Rate Ionizing Radiation And Simulated Microgravity, Amber M. Paul, Eliah G. Overbey, Willian A. Da Silveira, Nathaniel Szewczyk, Nina C. Nishiyama, Michael J. Pecaut, Sulekha Anand, Jonathan M. Galazka, Xiao Wen Mao

Publications

Using a ground-based model to simulate spaceflight [21-days of single-housed, hindlimb unloading (HLU) combined with continuous low-dose gamma irradiation (LDR, total dose of 0.04 Gy)], an in-depth survey of the immune and hematological systems of mice at 7-days post-exposure was performed. Collected blood was profiled with a hematology analyzer and spleens were analyzed by whole transcriptome shotgun sequencing (RNA-sequencing). The results revealed negligible differences in immune differentials. However, hematological system analyses of whole blood indicated large disparities in red blood cell differentials and morphology, suggestive of anemia. Murine Reactome networks indicated majority of spleen cells displayed differentially expressed genes (DEG) …

Machine Learning Classification Of Traumatic Brain Injury Patients Versus Healthy Controls Using Arterial Spin Labeled Perfusion Mri, Vanessa I. Grass

Dissertations, Theses, and Capstone Projects

Traumatic brain injury (TBI) is one of the most common causes of death and disability worldwide, yet accurate in vivo detection of TBI neuropathology remains challenging due to complexities in the structural and functional changes observed post-injury as well as limitations in conventional neuroimaging modalities. Although advanced neuroimaging techniques such as arterial spin labeling (ASL) can noninvasively assess cerebral blood flow (CBF) changes observed post-injury, this technique is underutilized in TBI research partly due to the low signal-to-noise-ratio (SNR) inherent in ASL imaging. The aim of the current study is to examine the use of machine learning, specifically a Support …

Explicit Training To Improve Affective Prosody Recognition In Adults With Acute Right Hemisphere Stroke, Alexandra Zezinka Durfee, Shannon M. Sheppard, Erin L. Meier, Lisa Bunker, Erjia Cui, Ciprian Crainiceanu, Argye E. Hillis

Communication Sciences and Disorders Faculty Articles and Research

Difficulty recognizing affective prosody (receptive aprosodia) can occur following right hemisphere damage (RHD). Not all individuals spontaneously recover their ability to recognize affective prosody, warranting behavioral intervention. However, there is a dearth of evidence-based receptive aprosodia treatment research in this clinical population. The purpose of the current study was to investigate an explicit training protocol targeting affective prosody recognition in adults with RHD and receptive aprosodia. Eighteen adults with receptive aprosodia due to acute RHD completed affective prosody recognition before and after a short training session that targeted proposed underlying perceptual and conceptual processes. Behavioral impairment and lesion characteristics were …

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

Honors Scholar Theses

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

Implementation Of A National Telestroke Program: A Unit-Based Staff Education Inititative, Leigh Ann Raymond

Master of Science in Nursing Scholarly Project

Abstract

A national telestroke program (NTSP) was implemented at a medical center in the latter half of 2020. Following two inpatient strokes, it was discovered that only 67 members of the 370-member inpatient nursing staff had been assigned the required online learning modules. A unit-based nursing educational initiative was developed utilizing available online learning modules to address the gaps in knowledge in recognizing acute stroke signs, symptoms and providing timely care. The educational initiative, however, supplemented and complimented the online learning modules by incorporating an in-person poster presentation on inpatient strokes that included a small group discussion of an inpatient …

Development Of A Novel Cognitive-Motor Dual Task Assessment Battery In Neurodegenerative Disease, Jason Longhurst

UNLV Theses, Dissertations, Professional Papers, and Capstones

Automaticity --- the ability to perform a task with directing attentional resources to its completion --- is commonly reduced among individuals with neurodegenerative diseases. These automaticity deficits result in impaired functional and daily activities and are sensitive to subtle, subclinical impairments. However, current measurement of automaticity by dual task paradigms is methodologically limited. In order to gain insight into the current state of the literature regarding cognitive-motor interference in symptomatic and prodromal neurodegenerative disease, the author of this dissertation conducted a scoping review (Chapter 1). To address the methodological limitations of current measurement of automaticity, a new measurement tool was …

The Mechanism Underlying Transient Weakness In Myotonia Congenita, Jessica H. Myers, Kirsten Denman, Chris Dupont, Ahmed A. Hawash, Kevin R. Novak, Andrew Koesters, Manfred Grabner, Anamika Dayal, Andrew A. Voss, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

In addition to the hallmark muscle stiffness, patients with recessive myotonia congenita (Becker disease) experience debilitating bouts of transient weakness that remain poorly understood despite years of study. We performed intracellular recordings from muscle of both genetic and pharmacologic mouse models of Becker disease to identify the mechanism underlying transient weakness. Our recordings reveal transient depolarizations (plateau potentials) of the membrane potential to -25 to -35 mV in the genetic and pharmacologic models of Becker disease. Both Na + and Ca 2+ currents contribute to plateau potentials. Na + persistent inward current (NaPIC) through Na V 1.4 channels is the …

A Mouse Model Of Huntington’S Disease Shows Altered Ultrastructure Of Transverse Tubules In Skeletal Muscle Fibers, Shannon H. Romer, Sabrina Metzger, Kristiana Peraza, Matthew C. Wright, D. Scott Jobe, Long-Sheng Song, Mark M. Rich, Brent D. Foy, Robert J. Talmadge, Andrew A. Voss

Neuroscience, Cell Biology & Physiology Faculty Publications

Huntington’s disease (HD) is a fatal and progressive condition with severe debilitating motor defects and muscle weakness. Although classically recognized as a neurodegenerative disorder, there is increasing evidence of cell autonomous toxicity in skeletal muscle. We recently demonstrated that skeletal muscle fibers from the R6/2 model mouse of HD have a decrease in specific membrane capacitance, suggesting a loss of transverse tubule (t-tubule) membrane in R6/2 muscle. A previous report also indicated that Cav1.1 current was reduced in R6/2 skeletal muscle, suggesting defects in excitation–contraction (EC) coupling. Thus, we hypothesized that a loss and/or disruption of the skeletal muscle t-tubule …

Long-Term Impacts Of Acute Stressor Exposure On Locus Coeruleus Function And Anxiety-Like Behavior In Rats, Olga Borodovitsyna

Graduate School of Biomedical Sciences Theses and Dissertations

Stress is a physiological state characterized by behavioral arousal that occurs during exposure to harmful or threatening stimuli, and usually facilitates an adaptive behavioral response. The persistence of stress sometimes causes it to become maladaptive, potentially contributing to disease development, including physiological complications with altered neuroendocrine signaling and impaired function of organ systems, and psychological conditions including depression and anxiety. Anxiety disorders in particular are associated with a history of stress and are the most common class of mental disorders, with a lifetime prevalence of 33.7% in the general population. The locus coeruleus (LC) is a major node in the …

Prenatal Maternal Mood Entropy Is Associated With Child Neurodevelopment, Mariann A. Howland, Curt A. Sandman, Elysia Poggi Davis, Hal S. Stern, Michael Phelan, Tallie Z. Baram, Laura M. Glynn

Psychology Faculty Articles and Research

Emerging evidence indicates that the predictability of signals early in life may influence the developing brain. This study examines links between a novel indicator of maternal mood dysregulation, mood entropy, and child neurodevelopmental outcomes. Associations between prenatal maternal mood entropy and child neurodevelopment were assessed in 2 longitudinal cohorts. Maternal mood was measured several times over pregnancy beginning as early as 15 weeks’ gestation. Shannon’s mood entropy was applied to distributions of mothers’ responses on mood questionnaires. Child cognitive and language development were evaluated at 2 and 6–9 years of age. Higher prenatal maternal mood entropy was associated with lower …

Neurophysiology Of Space Medicine: A Literature Review, Jose R. Velasquez

MEDI 9331 Scholarly Activities Clinical Years

Space medicine is becoming an essential and expanding clinical discipline. Acquiring a deeper and complete picture understanding of the multi-systemic response due to space on human health and function is essential to ensure the success of future space exploration. A comprehensive review of the literature was performed using PubMed and focused on the current neurophysiologic findings of the central nervous system’s response to space. Ground-based analogues, which mimic the effects of microgravity, and actual spaceflight studies have been used to analyze these physiologic adaptations to space. Overall, cerebellar, sensorimotor and vestibular brain regions seem to be affected the most. Through …

Glucocorticoid Receptor Antagonist Mifepristone Does Not Alter Innate Anxiety-Like Behavior In Genetically-Selected Marchigian Sardinian (Msp) Rats, Valentina Vozella, Bryan Cruz, Luis A. Natividad, Federica Benvenuti, Nazzareno Cannella, Scott Edwards, Eric P. Zorrilla, Roberto Ciccocioppo, Marisa Roberto

School of Graduate Studies Faculty Publications

Marchigian Sardinian alcohol-preferring (msP) rats serve as a unique model of heightened alcohol preference and anxiety disorders. Their innate enhanced stress and poor stress-coping strategies are driven by a genetic polymorphism of the corticotropin-releasing factor receptor 1 (CRF1) in brain areas involved in glucocorticoid signaling. The activation of glucocorticoid receptors (GRs) regulates the stress response, making GRs a candidate target to treat stress and anxiety. Here, we examined whether mifepristone, a GR antagonist known to reduce alcohol drinking in dependent rats, decreases innate symptoms of anxiety in msPs. Male and female msPs were compared to non-selected Wistar counterparts across three …

Aberrant Maturation Of The Uncinate Fasciculus Follows Exposure To Unpredictable Patterns Of Maternal Signals, Steven J. Granger, Laura M. Glynn, Curt A. Sandman, Steven L. Small, Andre Obenaus, David B. Keator, Tallie Z. Baram, Hal S. Stern, Michael A. Yassa, Elyssia Poggi Davis

Psychology Faculty Articles and Research

Across species, unpredictable patterns of maternal behavior are emerging as novel predictors of aberrant cognitive and emotional outcomes later in life. In animal models, exposure to unpredictable patterns of maternal behavior alters brain circuit maturation and cognitive and emotional outcomes. However, whether exposure to such signals in humans alters the development of brain pathways is unknown. In mother–child dyads, we tested the hypothesis that exposure to more unpredictable maternal signals in infancy is associated with aberrant maturation of corticolimbic pathways. We focused on the uncinate fasciculus, the primary fiber bundle connecting the amygdala to the orbitofrontal cortex and a key …

Assessment Of Major Depressive Disorders Through Neuroimaging Studies And Their Treatment Methods, Jevetha Vijayadasan, Diksha Raghunathan, Sivakumar Rajagopal, Rahul Soangra

Physical Therapy Faculty Articles and Research

Many mental disorders are caused due to improper regulation of the brain and depression is one such. It affects both children and adults and is very common among teenagers. There are many challenges clinicians face regarding the management of this disease. These challenges have prompted the development of various neuroimaging techniques that effectively diagnose the condition. The main techniques are Magnetic resonance imaging (MRI) and Positron emission tomography (PET) which have gained momentum over the years. Advanced MRI techniques help study certain regions of the brain such as hippocampus and amygdala. Effective treatments for depression include antidepressant medications and brain …

The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

β-N-methylamino-l-alanine (BMAA) is a nonproteinogenic amino acid that has been associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). BMAA has been found in human protein extracts; however, the mechanism by which it enters the proteome is still unclear. It has been suggested that BMAA is misincorporated at serine codons during protein synthesis, but direct evidence of its cotranslational incorporation is currently lacking. Here, using LC-MS–purified BMAA and several biochemical assays, we sought to determine whether any aminoacyl-tRNA synthetase (aaRS) utilizes BMAA as a substrate for aminoacylation. Despite BMAA's previously predicted misincorporation at serine …

Characterization Of Abin-1 In The Traumatically Injured Brain, Aaron Orellana, Alana C. Conti

Medical Student Research Symposium

Traumatic brain injury (TBI) is associated with chronic pain and persistent neuroinflammation. Opioids are often prescribed in order to relieve pain symptoms, but recent evidence suggests that their use negatively impacts the neuropathology of TBI leading to behavioral impairments and exacerbated neuroinflammation. The de-ubiquinating enzyme tumor necrosis factor alpha-induced protein (TNFAIP)3 or A20, inhibits the inflammatory signaling transcription factor nuclear factor (NF)-kB leading to attenuation of the inflammatory response. A20-binding inhibitor of nuclear factor kB (ABIN-1), which physically interacts with A20, also plays a role in the inhibition of NF-kB and is poorly researched in the central nervous system (CNS). …

Open Neuroscience Initiative, Austin Lim

College of Science and Health Full Text Publications

The Open Neuroscience Initiative is a free-to-use textbook

This project began as a means to overcoming the financial burden that face undergraduate neuroscience students when buying textbooks. By compiling and writing a completely free-to-access textbook that covers the foundations of a typical college introduction to neuroscience course, students would have one less obstacle to overcome in their educational career, allowing them to focus their valuable time and attention on learning rather than finances. To make this project a reality, I began with a humble tweet in May 2019 that managed to gain a tiny bit of traction among the neuroscience …

Genus Applications For Alzheimer's Disease Pathology, Whitney L Carter

Undergraduate Arts and Research Showcase

Estimates vary, but it is thought that 5.5 million Americans age 60 and up may be living with Alzheimer’s diseases (AD). AD is the most common type of dementia and is characterized by a decline in episodic memories, long-term memory, language, attention, and personality changes. The first symptoms can vary, but for most people memory is the first capacity to become impaired. However, symptoms can also be a decline in non-memory aspects of cognition like work-finding, vision/spatial issues, and impaired reasoning or judgement. AD is identified mainly by two histopathological features: extracellular plague of amyloid-beta protein and intracellular neuronal tangles …

Protocadherin-19 Expression And Function In Vertebrate Brain Review, Makana Mcguire

Williams Honors College, Honors Research Projects

For this project, a systematic review will be conducted on published studies on protocadherin-19 expression and function in vertebrate central nervous system development in the last 10 years. Protocadherin-19 (pcdh19) is a member of the cadherin superfamily. Cadherins are calcium-dependent cell adhesion molecules show to play important roles in vertebrate tissue development including the formation of the central nervous system. Understanding molecular and cellular mechanisms underlying the function of pcdh19 will help aid in understanding disease(s) caused by malfunction of this molecule, and lead to potential strategies for treatment. Data will be collected via online search of databases. The project …

Neural Stem Cell Metabolic Changes In The Presence Of Interferon-Gamma, Dylan Mckibben

Williams Honors College, Honors Research Projects

Spinal cord injury results in significant disability and health care costs due to an inability of the mature central nervous system to regenerate. One potential therapy would be implantation of neural stem cells to the injury site and stimulation of their differentiation to mature neurons. Previous work has shown that the cytokine interferon-gamma can promote this process; however, the signaling pathways induced in neural stem cells have not been well-defined. This proposal examines neural stem cell metabolic responses to signaling induced by interferon-gamma. Two questions will be answered: i) What specific metabolic pathway is activated to guide neural stem cell …

Effects Of Buprenorphine Treatment On Myelin Following Traumatic Brain Injury In A Rat Model, Jane Ryu

Theses and Dissertations

Traumatic brain injury (TBI) is a common phenomenon, accounting for significant cost and adverse health effects. While there is information about focal pathologies following TBI, knowledge of more diffuse processes is lacking, particularly regarding how analgesics affect this pathology. As Buprenorphine (Bup) is the most commonly used analgesic in experimental TBI models, the current study investigated the effects of the opioid analgesic Buprenorphine-sustained release-Lab (Bup-SR-Lab) on physiology and myelin alterations at 1d and 4w following central fluid percussion injury (cFPI) in adult male rats. Microscopic assessments were performed at 1 day and 4w post-injury. Myelin pathology was assessed by evaluating …

Pre-Clinical Advancements In Biomarkers, Tools, And Therapeutics For A Metabolic Neurodegenerative Disease, Zoë Simmons

Theses and Dissertations--Molecular and Cellular Biochemistry

Glycogen is the storage form of glucose and a highly important substrate for cellular metabolism. Characterization of the enzymes and mechanisms of glycogen metabolism began over 70 years ago and over the last 20 years, a previously unknown protein called laforin has emerged as an important contributor to glycogen metabolism homeostasis. Multiple labs demonstrated that laforin is a glycogen phosphatase and mutations in the gene encoding laforin cause the formation of aberrant glycogen-like aggregates called Lafora bodies (LBs). LBs are cytoplasmic, water-insoluble aggregates that drive neurodegeneration and early death in Lafora disease (LD) patients. The direct relationship between mutated laforin, …

Selective Gsk3b Deletion In Camk2a+ Forebrain Neurons Or Inhibition Via Tideglusib, Decreases Ethanol Consumption In C57bl/6j Mice, Sam Gottlieb, Andrew D. Van Der Vaart, Brennen O'Rourke, Michael F. Miles

Graduate Research Posters

Purpose: We previously identified glycogen synthase kinase-3 beta (Gsk3b) as a central member of a gene network highly regulated by acute ethanol in medial prefrontal cortex (mPFC) and associated with risk for alcohol dependence in humans. Further, we have demonstrated modulation of Gsk3b alters ethanol consumption in rodent models. GSK3B could thus represent a potential new therapeutic target for the treatment of alcohol use disorder (AUD). Here, we investigate the mechanisms of Gsk3b action in ethanol consumption and report preclinical evidence for the selective GSK3B inhibitor, tideglusib, as a therapeutic agent for AUD.

Methods: (1) Selective Cre-induced Gsk3b …

The Effect Of The Interaction Of Exercise Training And Isolation On The Serotonergic System Of App/Ps1 Mice, Bailey J. Dansby

Graduate Theses/Dissertations

Alzheimer’s disease (AD) is a complex neurodegenerative disease that is characterized by the deposition of amyloid beta (Ab) peptides and, consecutively, by a loss of memory and cognitive functions. The amyloid cascade hypothesis suggests that Ab deposition is the main pathogenic of AD. There is evidence that both changes in production and clearance of Ab may be involved in AD pathology. Past studies have shown that exercise training leads to an upregulation in proteins directly involved with Ab clearance. Chronic stress is thought to exacerbate AD pathology by increasing production of Ab. Studies have also demonstrated a link between serotonin …