Open Access. Powered by Scholars. Published by Universities.®

Neurosciences Commons™

Open Access. Powered by Scholars. Published by Universities.®

Medical Physiology

Institution
Keyword
Publication Year
Publication
Publication Type

Articles 31 - 60 of 135

Full-Text Articles in Neurosciences

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 Jun 2021

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 …


Myeloid Arginase 1 Insufficiency Exacerbates Amyloid-Β Associated Neurodegenerative Pathways And Glial Signatures In A Mouse Model Of Alzheimer’S Disease: A Targeted Transcriptome Analysis, Chao Ma, Jerry B. Hunt, Andrii Kovalenko, Huimin Liang, Maj-Linda B. Selenica, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee May 2021

Myeloid Arginase 1 Insufficiency Exacerbates Amyloid-Β Associated Neurodegenerative Pathways And Glial Signatures In A Mouse Model Of Alzheimer’S Disease: A Targeted Transcriptome Analysis, Chao Ma, Jerry B. Hunt, Andrii Kovalenko, Huimin Liang, Maj-Linda B. Selenica, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Brain myeloid cells, include infiltrating macrophages and resident microglia, play an essential role in responding to and inducing neurodegenerative diseases, such as Alzheimer’s disease (AD). Genome-wide association studies (GWAS) implicate many AD casual and risk genes enriched in brain myeloid cells. Coordinated arginine metabolism through arginase 1 (Arg1) is critical for brain myeloid cells to perform biological functions, whereas dysregulated arginine metabolism disrupts them. Altered arginine metabolism is proposed as a new biomarker pathway for AD. We previously reported Arg1 deficiency in myeloid biased cells using lysozyme M (LysM) promoter-driven deletion worsened amyloidosis-related neuropathology and behavioral impairment. However, …


Water Exchange Rate Across The Blood-Brain Barrier Is Associated With Csf Amyloid-Β 42 In Healthy Older Adults, Brian T. Gold, Xingfeng Shao, Tiffany L. Sudduth, Gregory A. Jicha, Donna M. Wilcock, Elayna R. Seago, Danny J. J. Wang May 2021

Water Exchange Rate Across The Blood-Brain Barrier Is Associated With Csf Amyloid-Β 42 In Healthy Older Adults, Brian T. Gold, Xingfeng Shao, Tiffany L. Sudduth, Gregory A. Jicha, Donna M. Wilcock, Elayna R. Seago, Danny J. J. Wang

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: We tested if water exchange across the blood-brain barrier (BBB), estimated with a noninvasive magnetic resonance imaging (MRI) technique, is associated with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and neuropsychological function.

METHODS: Forty cognitively normal older adults (67–86 years old) were scanned with diffusion‐prepared, arterial spin labeling (DP‐ASL), which estimates water exchange rate across the BBB (kw). Participants also underwent CSF draw and neuropsychological testing. Multiple linear regression models were run with kw as a predictor of CSF concentrations and neuropsychological scores.

RESULTS: In multiple brain regions, BBB kw was positively associated with CSF amyloid …


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 Apr 2021

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 Apr 2021

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 …


Neurophysiology Of Space Medicine: A Literature Review, Jose R. Velasquez Mar 2021

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 …


CertL Reduces C16 Ceramide, Amyloid-Β Levels, And Inflammation In A Model Of Alzheimer’S Disease, Simone M. Crivelli, Qian Luo, Jo A. A. Stevens, Caterina Giovagnoni, Daan Van Kruining, Gerard Bode, Sandra Den Hoedt, Barbara Hobo, Anna-Lena Scheithauer, Jochen Walter, Monique T. Mulder, Christopher Exley, Matthew Mold, Michelle M. Mielke, Helga E. De Vries, Kristiaan Wouters, Daniel L. A. Van Den Hove, Dusan Berkes, María Dolores Ledesma, Joost Verhaagen, Mario Losen, Erhard Bieberich, Pilar Martinez-Martinez Feb 2021

CertL Reduces C16 Ceramide, Amyloid-Β Levels, And Inflammation In A Model Of Alzheimer’S Disease, Simone M. Crivelli, Qian Luo, Jo A. A. Stevens, Caterina Giovagnoni, Daan Van Kruining, Gerard Bode, Sandra Den Hoedt, Barbara Hobo, Anna-Lena Scheithauer, Jochen Walter, Monique T. Mulder, Christopher Exley, Matthew Mold, Michelle M. Mielke, Helga E. De Vries, Kristiaan Wouters, Daniel L. A. Van Den Hove, Dusan Berkes, María Dolores Ledesma, Joost Verhaagen, Mario Losen, Erhard Bieberich, Pilar Martinez-Martinez

Physiology Faculty Publications

BACKGROUND: Dysregulation of ceramide and sphingomyelin levels have been suggested to contribute to the pathogenesis of Alzheimer's disease (AD). Ceramide transfer proteins (CERTs) are ceramide carriers which are crucial for ceramide and sphingomyelin balance in cells. Extracellular forms of CERTs co-localize with amyloid-β (Aβ) plaques in AD brains. To date, the significance of these observations for the pathophysiology of AD remains uncertain.

METHODS: A plasmid expressing CERTL, the long isoform of CERTs, was used to study the interaction of CERTL with amyloid precursor protein (APP) by co-immunoprecipitation and immunofluorescence in HEK cells. The recombinant CERTL protein …


Novel Influences Of Sex And Apoe Genotype On Spinal Plasticity And Recovery Of Function After Spinal Cord Injury, Lydia E. Strattan, Daimen R. Britsch, Chris M. Calulot, Rachel S. J. Maggard, Erin L. Abner, Lance A. Johnson, Warren J. Alilain Feb 2021

Novel Influences Of Sex And Apoe Genotype On Spinal Plasticity And Recovery Of Function After Spinal Cord Injury, Lydia E. Strattan, Daimen R. Britsch, Chris M. Calulot, Rachel S. J. Maggard, Erin L. Abner, Lance A. Johnson, Warren J. Alilain

Sanders-Brown Center on Aging Faculty Publications

Spinal cord injuries can abolish both motor and sensory function throughout the body. Spontaneous recovery after injury is limited and can vary substantially between individuals. Despite an abundance of therapeutic approaches that have shown promise in preclinical models, there is currently a lack of effective treatment strategies that have been translated to restore function after SCI in the human population. We hypothesized that sex and genetic background of injured individuals could impact how they respond to treatment strategies, presenting a barrier to translating therapies that are not tailored to the individual. One gene of particular interest is APOE, which has …


Novel Mammalian Models For Understanding And Treating Spinal Cord Injury, Michael B. Orr Jan 2021

Novel Mammalian Models For Understanding And Treating Spinal Cord Injury, Michael B. Orr

Theses and Dissertations--Physiology

Spinal cord injury (SCI) is devastating and often leaves the injured individual with persistent dysfunction. The injury persists because humans have poor wound repair and there are no pharmacologic treatments to induce wound repair after SCI. The continued efforts to discover therapeutic targets and develop treatments heavily relies on animal models. The purpose of this project is to develop and study novel mammalian models of SCI to provide insights for the development and effective implementation of SCI therapies.

Lab mice (Mus musculus) are a powerful tool for recapitulating the progression and persistent damage evident in human SCI, but …


Electrophysiological And Imaging Calcium Biomarkers Of Aging In Male And Female 5×Fad Mice, Adam O. Ghoweri, Lara Ouillette, Hilaree N. Frazier, Katie L. Anderson, Ruei-Lung Lin, John C. Gant, Rachel Parent, Shannon Moore, Geoffrey G. Murphy, Olivier Thibault Dec 2020

Electrophysiological And Imaging Calcium Biomarkers Of Aging In Male And Female 5×Fad Mice, Adam O. Ghoweri, Lara Ouillette, Hilaree N. Frazier, Katie L. Anderson, Ruei-Lung Lin, John C. Gant, Rachel Parent, Shannon Moore, Geoffrey G. Murphy, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: In animal models and tissue preparations, calcium dyshomeostasis is a biomarker of aging and Alzheimer's disease that is associated with synaptic dysfunction, neuritic pruning, and dysregulated cellular processes. It is unclear, however, whether the onset of calcium dysregulation precedes, is concurrent with, or is the product of pathological cellular events (e.g., oxidation, amyloid-β production, and neuroinflammation). Further, neuronal calcium dysregulation is not always present in animal models of amyloidogenesis, questioning its reliability as a disease biomarker.

OBJECTIVE: Here, we directly tested for the presence of calcium dysregulation in dorsal hippocampal neurons in male and female 5×FAD mice on …


Oral Gavage Delivery Of Stable Isotope Tracer For In Vivo Metabolomics, Holden C. Williams, Margaret A. Piron, Grant K. Nation, Adeline E. Walsh, Lyndsay E. A. Young, Ramon C. Sun, Lance A. Johnson Dec 2020

Oral Gavage Delivery Of Stable Isotope Tracer For In Vivo Metabolomics, Holden C. Williams, Margaret A. Piron, Grant K. Nation, Adeline E. Walsh, Lyndsay E. A. Young, Ramon C. Sun, Lance A. Johnson

Sanders-Brown Center on Aging Faculty Publications

Stable isotope-resolved metabolomics (SIRM) is a powerful tool for understanding disease. Advances in SIRM techniques have improved isotopic delivery and expanded the workflow from exclusively in vitro applications to in vivo methodologies to study systemic metabolism. Here, we report a simple, minimally-invasive and cost-effective method of tracer delivery to study SIRM in vivo in laboratory mice. Following a brief fasting period, we orally administered a solution of [U-13C] glucose through a blunt gavage needle without anesthesia, at a physiological dose commonly used for glucose tolerance tests (2 g/kg bodyweight). We defined isotopic enrichment in plasma and tissue at …


Effects Of Neuronic Shutter Observed In The Eeg Alpha Rhythm, Kevin E. Alexander, Justin R. Estepp, Sherif M. Elbasiouny Sep 2020

Effects Of Neuronic Shutter Observed In The Eeg Alpha Rhythm, Kevin E. Alexander, Justin R. Estepp, Sherif M. Elbasiouny

Neuroscience, Cell Biology & Physiology Faculty Publications

The posterior alpha (α) rhythm, seen in human electroencephalogram (EEG), is posited to originate from cycling inhibitory/excitatory states of visual relay cells in the thalamus. These cycling states are thought to lead to oscillating visual sensitivity levels termed the “neuronic shutter effect.” If true, perceptual performance should be predictable by observed α phase (of cycling inhibitory/excitatory states) relative to the timeline of afferentiation onto the visual cortex. Here, we tested this hypothesis by presenting contrast changes at near perceptual threshold intensity through closed eyelids to 20 participants (balanced for gender) during times of spontaneous α oscillations. To more accurately and …


Conditional Loss Of Engrailed 1/2 In Rhombic Lip-Derived Neurons Increases Intrinsic Rhythmicity And Decreases Overall Variability Of Eupneic Respiration, Angela P. Taylor Sep 2020

Conditional Loss Of Engrailed 1/2 In Rhombic Lip-Derived Neurons Increases Intrinsic Rhythmicity And Decreases Overall Variability Of Eupneic Respiration, Angela P. Taylor

Theses and Dissertations (ETD)

Evidence for a cerebellar role during cardiopulmonary challenges has long been established, but investigation into cerebellar involvement in eupneic breathing has been inconclusive. Given the view of the cerebellum (CRB) as a temporally coordinating structure, any investigation into the CRB during respiration must evaluate rhythm and variability of the respiratory sequence. In this study, we chose an elegant model of cerebellar neuropathology, Atoh1-En1/2 CKO, where mutant animals have conditional loss of the developmental patterning gene Engrailed 1/2 in rhombic lip-lineage neurons and exhibit a proportional scaling-down of neuron number in hypoplastic lobules of the CRB. We utilized whole-body unrestrained plethysmography …


Therapeutic Trem2 Activation Ameliorates Amyloid-Beta Deposition And Improves Cognition In The 5xfad Model Of Amyloid Deposition, Brittani R. Price, Tiffany L. Sudduth, Erica M. Weekman, Sherika Johnson, Danielle Hawthorne, Abigail E. Woolums, Donna M. Wilcock Aug 2020

Therapeutic Trem2 Activation Ameliorates Amyloid-Beta Deposition And Improves Cognition In The 5xfad Model Of Amyloid Deposition, Brittani R. Price, Tiffany L. Sudduth, Erica M. Weekman, Sherika Johnson, Danielle Hawthorne, Abigail E. Woolums, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Triggering receptor expressed on myeloid cell-2 (TREM2) is a lipid and lipoprotein binding receptor expressed by cells of myeloid origin. Homozygous TREM2 mutations cause early onset progressive presenile dementia while heterozygous, point mutations triple the risk of Alzheimer's disease (AD). Although human genetic findings support the notion that loss of TREM2 function exacerbates neurodegeneration, it is not clear whether activation of TREM2 in a disease state would result in therapeutic benefits. To determine the viability of TREM2 activation as a therapeutic strategy, we sought to characterize an agonistic Trem2 antibody (AL002a) and test its efficacy and mechanism of action …


The Role Of Central Ace2 And Nrf2 In Sympatho-Excitation: Responses To Central Angiotensin Ii, Anyun Ma May 2020

The Role Of Central Ace2 And Nrf2 In Sympatho-Excitation: Responses To Central Angiotensin Ii, Anyun Ma

Theses & Dissertations

Sympatho-excitation is a key characteristic in cardiovascular diseases such as chronic heart failure (CHF) and primary Hypertension (HTN). Evidence suggests that increased sympathetic tone is closely related to activation of the Renin-Angiotensin-Aldosterone system (RAAS) in the central nervous system. An underlying mechanism for sympatho-excitation is thought to be oxidative stress resulting from Angiotensin II (AngII) type 1 receptor (AT1R) activation. Over the past several decades, pharmacological targeting of components of the RAAS have been used as standard therapy in CHF and HTN. However, additional therapeutic strategies are necessary to control these diseases. Oxidative stress is regulated, in part, by the …


Depressed Neuromuscular Transmission Causes Weakness In Mice Lacking Bk Potassium Channels, Xueyong Wang, Steven R.A. Burke, Robert J. Talmadge, Andrew A. Voss, Mark M. Rich May 2020

Depressed Neuromuscular Transmission Causes Weakness In Mice Lacking Bk Potassium Channels, Xueyong Wang, Steven R.A. Burke, Robert J. Talmadge, Andrew A. Voss, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Mice lacking functional large-conductance voltage- and Ca2+-activated K+ channels (BK channels) are viable but have motor deficits including ataxia and weakness. The cause of weakness is unknown. In this study, we discovered, in vivo, that skeletal muscle in mice lacking BK channels (BK−/−) was weak in response to nerve stimulation but not to direct muscle stimulation, suggesting a failure of neuromuscular transmission. Voltage-clamp studies of the BK−/− neuromuscular junction (NMJ) revealed a reduction in evoked endplate current amplitude and the frequency of spontaneous vesicle release compared with WT littermates. Responses to 50-Hz stimulation indicated a reduced probability of vesicle release …


Acute Disseminated Encephalomyelitis, Ashan Hatharasinghe, Hossein Akhondi, Don Pepito Apr 2020

Acute Disseminated Encephalomyelitis, Ashan Hatharasinghe, Hossein Akhondi, Don Pepito

HCA Healthcare Journal of Medicine

Introduction: Acute Disseminated Encephalomyelitis (ADEM) is a rare autoimmune demyelinating disorder of the central nervous system. Clinical manifestations include encephalopathy, motor deficits, ataxia, and meningeal signs. In most cases, ADEM is preceded by either vaccination or viral illness. Here, we present a case with neither of the two predisposing elements.

Discussion: A 28-year-old Hispanic female presenting with substance use and suicidal ideation was placed on an involuntary psychiatric hold, started on olanzapine and scheduled for a psychiatric facility transfer. The following day, she was noted to have neurological deficits when ambulating. Computed tomography of the brain showed a right frontal …


Anxiety In Alzheimer's Disease, Zachary Cooper Apr 2020

Anxiety In Alzheimer's Disease, Zachary Cooper

Senior Honors Theses

Researchers familiar with Alzheimer’s disease have often noted the presence of comorbid anxiety symptomatology. Likewise, the occurrence of anxiety before the development of Alzheimer’s disease has been prevalent enough to warrant attention. This review seeks to elaborate on the pathophysiology behind these two conditions, and to accentuate overlapping aspects that promote a causal relationship between these two pathologies on the macroscopic and cellular levels. Subsequent evidence will show that these pathologies are not independent of each other, and that cellular mechanisms of pathology hint at their interrelatedness. Areas requiring further research that would clarify the relationship between Clinical Anxiety and …


Covid 19 What You Need To Know, Dawn P. Wooley, Giancarlo Mariani, Craig Woolley, Laura M. Luehrmann Apr 2020

Covid 19 What You Need To Know, Dawn P. Wooley, Giancarlo Mariani, Craig Woolley, Laura M. Luehrmann

Neuroscience, Cell Biology & Physiology Faculty Publications

This is the first presentation in the new Shelter-in-Place lecture series. This first lecture is two-fold. First, it covers the basics of the COVID-19 virus including: how it spreads, possible origin, and other pertinent information. This portion of the presentation was followed by an overview of the international recruitment efforts in response to the virus, including: student perspectives, recruitment methods, and other important information.


Sciatic Nerve Cut And Repair Using Fibrin Glue In Adult Mice, Erica T. Akhter, Travis M. Rotterman, Arthur W. English, Francisco J. Alvarez Sep 2019

Sciatic Nerve Cut And Repair Using Fibrin Glue In Adult Mice, Erica T. Akhter, Travis M. Rotterman, Arthur W. English, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Peripheral nerve injury (PNI) is an excellent model for studying neural responses to injury and elucidating the mechanisms that can facilitate axon regeneration. As such, several animal models have been employed to study regenerative mechanisms after PNI, including Aplysia, zebrafish, rabbits, cats and rodents. This protocol describes how to perform a sciatic nerve injury and repair in mice, one of the most frequently used models to study mechanisms that facilitate recovery after PNI, and that takes advantage of the availability of many genetic models. In this protocol, we describe a method for using fibrin glue to secure the proximal …


Self-Directed Down-Regulation Of Auditory Cortex Activity Mediated By Real-Time Fmri Neurofeedback Augments Attentional Processes, Resting Cerebral Perfusion, And Auditory Activation, Matthew Sherwood, Jason G. Parker, Emily E. Diller, Subhashini Ganapathy, Kevin B. Bennett, Carlos R. Esquivel, Jeremy T. Nelson Jul 2019

Self-Directed Down-Regulation Of Auditory Cortex Activity Mediated By Real-Time Fmri Neurofeedback Augments Attentional Processes, Resting Cerebral Perfusion, And Auditory Activation, Matthew Sherwood, Jason G. Parker, Emily E. Diller, Subhashini Ganapathy, Kevin B. Bennett, Carlos R. Esquivel, Jeremy T. Nelson

Neuroscience, Cell Biology & Physiology Faculty Publications

In this work, we investigated the use of real-time functional magnetic resonance imaging (fMRI) with neurofeedback training (NFT) to teach volitional down-regulation of the auditory cortex (AC) using directed attention strategies as there is a growing interest in the application of fMRI-NFT to treat neurologic disorders. Healthy participants were separated into two groups: the experimental group received real feedback regarding activity in the AC; the control group was supplied sham feedback yoked from a random participant in the experimental group and matched for fMRI-NFT experience. Each participant underwent five fMRI-NFT sessions. Each session contained 2 neurofeedback runs where participants completed …


Initial Characterization Of The Indole-3-Carboxamide Bic-154 As A Fast Onset And Reversible Orai Channel Blocker, Tetyana Zhelay, Kalina Szteyn, Elisa Liardo, Jae Eun Cheong, Steffi Koerner, Anil Ekkati, Lijun Sun, J. Ashot Kozak Feb 2019

Initial Characterization Of The Indole-3-Carboxamide Bic-154 As A Fast Onset And Reversible Orai Channel Blocker, Tetyana Zhelay, Kalina Szteyn, Elisa Liardo, Jae Eun Cheong, Steffi Koerner, Anil Ekkati, Lijun Sun, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

Calcium ion elevations are required for human T-lymphocyte proliferation in response to antigen recognition by a T-cell receptor. Calcium influx through the plasma membrane is necessary for efficient T-cell proliferation and effector function. The calcium channels responsible for Ca2+ influx in lymphocytes have been identified and Orai interacting with ER Ca2+ sensor STIM were shown to be crucial for persistent calcium mobilization. Loss-of-function mutations in Orai1 or STIM1 result in severe combined immunodeficiency (SCID) with muscle hypotonia. Suppression of calcium influx through Orai/STIM channels gives rise to various lymphoproliferative defects. Thus, deletion of Orai or STIM in mice results in …


The Migration And Developmental Remodeling Of Intrinsic Interneurons In Visual Thalamus And The Role Of Retinal Signaling., Naomi E. Charalambakis Dec 2018

The Migration And Developmental Remodeling Of Intrinsic Interneurons In Visual Thalamus And The Role Of Retinal Signaling., Naomi E. Charalambakis

Electronic Theses and Dissertations

The dorsal lateral geniculate nucleus (dLGN) of the mouse is a model system to study the development of thalamic circuitry. While most studies focus on relay neurons of dLGN, little is known about the factors regulating the development of the other principal cell type, intrinsic interneurons. To date, the targeting and migratory path of dLGN interneurons as well as their morphological development remains unclear. Here we examined whether the migration, structure, and function of interneurons relies on retinal signaling. We took a loss-of-function approach and crossed GAD67-GFP mice, which express green fluorescent protein (GFP) in dLGN interneurons, with math5 nulls …


Distinct White Matter Changes Associated With Cerebrospinal Fluid Amyloid-Β1-42 And Hypertension, Omar M. Al-Janabi, Christopher A. Brown, Ahmed A. Bahrani, Erin L. Abner, Justin M. Barber, Brian T. Gold, Larry B. Goldstein, Richard R. Murphy, Peter T. Nelson, Nathan F. Johnson, Leslie M. Shaw, Charles D. Smith, John Q. Trojanowski, Donna M. Wilcock, Gregory A. Jicha Nov 2018

Distinct White Matter Changes Associated With Cerebrospinal Fluid Amyloid-Β1-42 And Hypertension, Omar M. Al-Janabi, Christopher A. Brown, Ahmed A. Bahrani, Erin L. Abner, Justin M. Barber, Brian T. Gold, Larry B. Goldstein, Richard R. Murphy, Peter T. Nelson, Nathan F. Johnson, Leslie M. Shaw, Charles D. Smith, John Q. Trojanowski, Donna M. Wilcock, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Alzheimer's disease (AD) pathology and hypertension (HTN) are risk factors for development of white matter (WM) alterations and might be independently associated with these alterations in older adults.

OBJECTIVE: To evaluate the independent and synergistic effects of HTN and AD pathology on WM alterations.

METHODS: Clinical measures of cerebrovascular disease risk were collected from 62 participants in University of Kentucky Alzheimer's Disease Center studies who also had cerebrospinal fluid (CSF) sampling and MRI brain scans. CSF Aβ1-42 levels were measured as a marker of AD, and fluid-attenuated inversion recovery imaging and diffusion tensor imaging were obtained to assess …


Repetitive Transcranial Electrical Stimulation Induces Quantified Changes In Resting Cerebral Perfusion Measured From Arterial Spin Labeling, Matthew Sherwood, Aaron T. Madaris, Casserly R. Mullenger, R. Andy Mckinley Sep 2018

Repetitive Transcranial Electrical Stimulation Induces Quantified Changes In Resting Cerebral Perfusion Measured From Arterial Spin Labeling, Matthew Sherwood, Aaron T. Madaris, Casserly R. Mullenger, R. Andy Mckinley

Neuroscience, Cell Biology & Physiology Faculty Publications

The use of transcranial electrical stimulation (TES) as a method to augment neural activity has increased in popularity in the last decade and a half. The specific application of TES to the left prefrontal cortex has been shown to produce broad cognitive effects; however, the neural mechanisms underlying these effects remain unknown. In this work, we evaluated the effect of repetitive TES on cerebral perfusion. Stimulation was applied to the left prefrontal cortex on three consecutive days, and resting cerebral perfusion was quantified before and after stimulation using arterial spin labeling. Perfusion was found to decrease significantly more in a …


Propofol Inhibits The Voltage-Gated Sodium Channel Nachbac At Multiple Sites., Yali Wang, Elaine Yang, Marta M. Wells, Vasyl Bondarenko, Kellie Woll, Vincenzo Carnevale, Daniele Granata, Michael L. Klein, Roderic G. Eckenhoff, William P. Dailey, Manuel Covarrubias, Pei Tang, Yan Xu Sep 2018

Propofol Inhibits The Voltage-Gated Sodium Channel Nachbac At Multiple Sites., Yali Wang, Elaine Yang, Marta M. Wells, Vasyl Bondarenko, Kellie Woll, Vincenzo Carnevale, Daniele Granata, Michael L. Klein, Roderic G. Eckenhoff, William P. Dailey, Manuel Covarrubias, Pei Tang, Yan Xu

Department of Neuroscience Faculty Papers

Voltage-gated sodium (NaV) channels are important targets of general anesthetics, including the intravenous anesthetic propofol. Electrophysiology studies on the prokaryotic NaV channel NaChBac have demonstrated that propofol promotes channel activation and accelerates activation-coupled inactivation, but the molecular mechanisms of these effects are unclear. Here, guided by computational docking and molecular dynamics simulations, we predict several propofol-binding sites in NaChBac. We then strategically place small fluorinated probes at these putative binding sites and experimentally quantify the interaction strengths with a fluorinated propofol analogue, 4-fluoropropofol. In vitro and in vivo measurements show that 4-fluoropropofol and propofol have similar effects …


Gender- And Region-Specific Changes In Estrogen Signaling In Aging Rat Brain Mitochondria, Christopher M. Evola, Tanner L. Hudson, Luping Huang, Adrian M. Corbett, Debra A. Mayes Aug 2018

Gender- And Region-Specific Changes In Estrogen Signaling In Aging Rat Brain Mitochondria, Christopher M. Evola, Tanner L. Hudson, Luping Huang, Adrian M. Corbett, Debra A. Mayes

Neuroscience, Cell Biology & Physiology Faculty Publications

Recently epidemiological studies suggest females lose neuroprotection from neurodegenerative diseases as they go through menopause. It has been hypothesized that this neuroprotection is hormone‐dependent. The current study characterized cell signaling molecules downstream of estrogen receptor beta that are known to play a role in memory, PKC, ERK, and connexin‐43, in regions of the brain associated with memory decline in an attempt to elucidate significant changes that occur post‐estrus. Total whole cell lysates were compared to isolated mitochondrial protein because mitochondrial function is known to be altered during aging. As hypothesized, protein concentrations differed depending on age, gender, and brain region. …


Volitional Down-Regulation Of The Primary Auditory Cortex Via Directed Attention Mediated By Real-Time Fmri Neurofeedback, Matthew Sherwood, Jason G. Parker, Emily E. Diller, Subhashini Ganapathy, Kevin B. Bennett, Jeremy T. Nelson Jul 2018

Volitional Down-Regulation Of The Primary Auditory Cortex Via Directed Attention Mediated By Real-Time Fmri Neurofeedback, Matthew Sherwood, Jason G. Parker, Emily E. Diller, Subhashini Ganapathy, Kevin B. Bennett, Jeremy T. Nelson

Neuroscience, Cell Biology & Physiology Faculty Publications

The present work assessed the efficacy of training volitional down-regulation of the primary auditory cortex (A1) based on real-time functional magnetic resonance imaging neurofeedback (fMRI-NFT). A1 has been shown to be hyperactive in chronic tinnitus patients, and has been implicated as a potential source for the tinnitus percept. 27 healthy volunteers with normal hearing underwent 5 fMRI-NFT sessions: 18 received real neurofeedback and 9 sham neurofeedback. Each session was composed of a simple auditory fMRI followed by 2 runs of A1 fMRI-NFT. The auditory fMRI alternated periods of no auditory with periods of white noise stimulation at 90 dB. A1 …


Spinal Control Of Locomotion: Individual Neurons, Their Circuits And Functions, Marie-Pascale Côté, Lynda M. Murray, Maria Knikou Jun 2018

Spinal Control Of Locomotion: Individual Neurons, Their Circuits And Functions, Marie-Pascale Côté, Lynda M. Murray, Maria Knikou

Publications and Research

Systematic research on the physiological and anatomical characteristics of spinal cord interneurons along with their functional output has evolved for more than one century. Despite significant progress in our understanding of these networks and their role in generating and modulating movement, it has remained a challenge to elucidate the properties of the locomotor rhythm across species. Neurophysiological experimental evidence indicates similarities in the function of interneurons mediating afferent information regarding muscle stretch and loading, being affected by motor axon collaterals and those mediating presynaptic inhibition in animals and humans when their function is assessed at rest. However, significantly different muscle …


Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin May 2018

Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin

Senior Honors Theses

The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research is …