Medical Neurobiology Commons^™

An Overview Of Leber’S Hereditary Optic Neuropathy, Matthew R. Dalton

The Kabod

Typically affecting males ranging from 20 to 24 years of age, Leber’s Hereditary Optic Neuropathy (LHON) is a disorder that is characterized by an acute loss of central vision. Although a heritable disease, LHON does not follow the patterns of classical Mendelian genetics. In fact, one of the most striking characteristics of LHON is that the disease is virtually always inherited maternally. Unlike most genetic disorders that result from a mutation in genomic DNA, LHON is caused by a mutation in the genetic information of mitochondria (mtDNA). Currently there is no treatment for LHON. Despite this, pharmaceutical interventions and contemporary …

Isoflurane Inhibits Synaptic Vesicle Exocytosis Through Reduced Ca2+ Influx, Not Ca2+-Exocytosis Coupling, Joel Baumgart, Zhen-Yu Zhou, Masato Hara, Daniel Cook, Michael Hoppa

Dartmouth Scholarship

Identifying presynaptic mechanisms of general anesthetics is critical to understanding their effects on synaptic transmission. We show that the volatile anesthetic isoflurane inhibits synaptic vesicle (SV) exocytosis at nerve terminals in dissociated rat hippocampal neurons through inhibition of presynaptic Ca2+ influx without significantly altering the Ca2+ sensitivity of SV exocytosis. A clinically relevant concentration of isoflurane (0.7 mM) inhibited changes in [Ca2+]i driven by single action potentials (APs) by 25 ± 3%, which in turn led to 62 ± 3% inhibition of single AP-triggered exocytosis at 4 mM extracellular Ca2+ ([Ca2+]e). Lowering external Ca2+ to match the isoflurane-induced reduction in …

The Role Of Glutaminase 1 In Hiv-1 Associated Neurocognitive Disorders And In Brain Development, Yi Wang

Theses & Dissertations

Glutaminase is the enzyme that converts glutamine into glutamate, which serves as a key excitatory neurotransmitter and one of the energy providers for cellular metabolism. Glutamate is essential for proper brain functioning but at excess levels, it is neurotoxic and has a key role in the pathogenesis of various neurodegenerative diseases, including HIV-1 associated neurocognitive disorders (HAND). However, the detailed mechanism of glutamate-mediated neurotoxicity remains unclear. In part I, we identified the regulation of glutaminase 1 (GLS1) in the central nervous system (CNS) of HAND animal models including HIV-Tat transgenic (Tg) mouse and HIVE-SCID mouse, since GLS1 is the dominant …

The Effect Of Sleep On Perceptual Learning And Memory Consolidation, Vanessa Claire Irsik

UNLV Theses, Dissertations, Professional Papers, and Capstones

An ability to segregate speech accurately is essential given that most auditory environments contain other overlapping conversations or environmental noise. While perceiving speech among background noise can be difficult in and of itself, those with hearing impairments can experience considerable difficulty. While training has been shown to benefit perceptual segregation of trained sounds, it is unclear how such training transfers to sounds not included in a training regimen. The current study aimed to address this question by training listeners on a portion of sounds during a vowel segregation task, and subsequently testing on both the trained sounds and untrained sounds. …

Plastin 3 Expression Does Not Modify Spinal Muscular Atrophy Severity In The ∆7 Sma Mouse, Vicki L. Mcgovern, Aurelie Massoni-Laporte, Xueyong Wang, Thanh T. Le, Hao T. Le, Mark M. Rich, Arthur H. M. Burghes

Neuroscience, Cell Biology & Physiology Faculty Publications

Spinal muscular atrophy is caused by loss of the SMN1 gene and retention of SMN2. TheSMN2 copy number inversely correlates with phenotypic severity and is a modifier of disease outcome. The SMN2 gene essentially differs from SMN1 by a single nucleotide in exon 7 that modulates the incorporation of exon 7 into the final SMN transcript. The majority of the SMN2transcripts lack exon 7 and this leads to a SMN protein that does not effectively oligomerize and is rapidly degraded. However theSMN2 gene does produce some full-length SMN and theSMN2 copy number along with how …

Taranis Functions With Cyclin A And Cdk1 In A Novel Arousal Center To Control Sleep In Drosophila., Dinis J.S. Afonso, Die Liu, Daniel R. Machado, Huihui Pan, James E.C. Jepson, Dragana Rogulja, Kyunghee Koh

Department of Neuroscience Faculty Papers

Sleep is an essential and conserved behavior whose regulation at the molecular and anatomical level remains to be elucidated. Here, we identify TARANIS (TARA), a Drosophila homolog of the Trip-Br (SERTAD) family of transcriptional coregulators, as a molecule that is required for normal sleep patterns. Through a forward-genetic screen, we isolated tara as a novel sleep gene associated with a marked reduction in sleep amount. Targeted knockdown of tara suggests that it functions in cholinergic neurons to promote sleep. tara encodes a conserved cell-cycle protein that contains a Cyclin A (CycA)-binding homology domain. TARA regulates CycA protein levels and genetically …

A Comparison Of The Effects Of Different Doses Of Gabab Receptor Ligands On Spatial Learning And Memory And Memory Flexibility, Chelcie Heaney

UNLV Theses, Dissertations, Professional Papers, and Capstones

The principal inhibitory neurotransmitter in the brain, gamma amino-butyric acid (GABA), mediates several types of learning and memory. Of the two main receptor subtypes for GABA, the in vivo role of GABAB receptor in learning and memory is less well characterized and the current data often conflict. Based on the current literature, it is unclear, for instance, whether enhancing GABAergic activity via the GABAB receptor could be beneficial for or detrimental to learning and memory. Hippocampally-dependent learning and memory tasks are of particular interest due to their clinical relevance to patients with schizophrenia or Alzheimer’s disease, who exhibit impaired performance …

Functional Capacity In Schizophrenia: Relationship Among Effort, Reinforcement Learning And Self-Beliefs, Sally J. Vogel

UNLV Theses, Dissertations, Professional Papers, and Capstones

Individuals with schizophrenia exhibit a wide range of complex neurocognitive, psychiatric and behavioral impairments. Recent research suggests that this complex array of symptoms can be at least partially accounted for by dysfunction in more basic mechanisms, such as the ability to learn from positive and negative reinforcement, or the ability to exert adequate effort when completing simple tasks. Evidence also suggests that deficits in these basic mechanisms may contribute to more complex symptoms, such as functional impairment. Also, the relationship between neurocognitive deficits and functional impairment has been found to be mediated by defeatist performance beliefs. However, studies have not …

Early Inflammatory Mediator Gene Expression In Two Models Of Traumatic Brain Injury: Ex Vivo Cortical Slice In Mice And In Vivo Cortical Impact In Piglets, David J. Graber, Beth A. Costine, William F. Hickey

Dartmouth Scholarship

Background: The immunological response during the first 24 hours after traumatic brain injury (TBI) may be a critical therapeutic interval for limiting the secondary neuronal damage that is influenced by enhanced inflammatory mediator expression.

Methods: To gain further insight of the early injury response, we examined the expression of several inflammatory genes by real-time qPCR as a function of time or distance from injury in two distinct mammalian models: an ex vivo mouse cortical slice injury system and an in vivo piglet model of brain injury.

The Preparatory Set: A Novel Approach To Understanding Stress, Trauma, And The Bodymind Therapies, Peter Payne, Mardi A. Crane-Godreau

Dartmouth Scholarship

Basic to all motile life is a differential approach/avoid response to perceived features of environment. The stages of response are initial reflexive noticing and orienting to the stimulus, preparation, and execution of response. Preparation involves a coordination of many aspects of the organism: muscle tone, posture, breathing, autonomic functions, motivational/emotional state, attentional orientation, and expectations. The organism organizes itself in relation to the challenge. We propose to call this the "preparatory set" (PS). We suggest that the concept of the PS can offer a more nuanced and flexible perspective on the stress response than do current theories. We also hypothesize …

Brain Blast 2015 Speakers Poster, Annie Leslie

Brain Blast

Poster from UNE's Brain Blast 2015 listing the expected presenters at this event.*

Method Of Treating Parkinson's Disease In Humans By Convection-Enhanced Infusion Of Glial Cell-Line Derived Neurotrophic Factor To The Putamen, Stephen S. Gill, Don M. Gash, Greg A. Gerhardt

Neuroscience Faculty Patents

A method of treating Parkinson's disease in humans is disclosed, wherein glial cell-line derive neurotrophic factor (GDNF) is chronically administered directly to one or both putamen of a human in need of treatment thereof via convection-enhanced infusion using at least one implantable pump and at least one catheter. In one aspect of the present invention the GDNF is infused directly into one or both putamen through one or more indwelling intraparenchymal multiport brain catheters connected to one or more implantable pumps wherein the flow rate is pulsed.

Method Of Treating Parkinson's Disease In Humans By Convection-Enhanced Infusion Of Glial Cell-Line Derived Neurotrophic Factor To The Putamen, Stephen S. Gill, Don M. Gash, Greg A. Gerhardt

Neuroscience Faculty Patents

A method of treating Parkinson's disease in humans is disclosed, wherein glial cell-line derive neurotrophic factor (GDNF) is chronically administered directly to one or both putamen of a human in need of treatment thereof via convection-enhanced infusion using at least one implantable pump and at least one catheter. In one aspect of the present invention the GDNF is infused directly into one or both putamen through one or more indwelling intraparenchymal mutitiport brain catheters connected to one or more implantable pumps wherein the flow rate is pulsed.

Exposure To Kynurenic Acid During Adolescence Increases Sign-Tracking And Impairs Long-Term Potentiation In Adulthood, Nicole E. Deangeli, Travis P. Todd, Stephen E. Chang, Hermes H. Yeh, Pamela W. Yeh, David J. Bucci

Dartmouth Scholarship

Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently, there are few treatments for persons with a dual diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA), a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and …

The Piriform, Perirhinal, And Entorhinal Cortex In Seizure Generation., Marta S Vismer, Patrick A Forcelli, Mark D Skopin, Karen Gale, Mohamad Z. Koubeissi

Neurology Faculty Publications

Understanding neural network behavior is essential to shed light on epileptogenesis and seizure propagation. The interconnectivity and plasticity of mammalian limbic and neocortical brain regions provide the substrate for the hypersynchrony and hyperexcitability associated with seizure activity. Recurrent unprovoked seizures are the hallmark of epilepsy, and limbic epilepsy is the most common type of medically-intractable focal epilepsy in adolescents and adults that necessitates surgical evaluation. In this review, we describe the role and relationships among the piriform (PIRC), perirhinal (PRC), and entorhinal cortex (ERC) in seizure-generation and epilepsy. The inherent function, anatomy, and histological composition of these cortical regions are …

Neuronal Migration: How Do You Build A Brain?, Sravya Uppalapati

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Senior biology major Alex Burkard is working in the Walsh Neurodevelopment Laboratory at VCU to help answer the question, ‘How do you build a brain?’ Burkard is researching neuronal migration in Zebrafish and how cellular polarity affects hindbrain development.

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 …

Axon Initial Segment Stability In Multiple Sclerosis, Suneel K. Thummala

Theses and Dissertations

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by inflammation and demyelination. In addition to these hallmark features, MS also presents with axonal pathology, which is likely responsible for the signs and symptoms of the disease. Although prominent in MS, axonal pathology is frequently considered a consequence of demyelination and not a primary event. This conclusion is consistent with demyelination inducing the loss of specific axonal domains, known as the nodes of Ranvier that are responsible for the propagation of action potentials along the axon. In contrast, we propose that axonal pathology associated with MS …

Appropriate Timing Of Fluoxetine And Statin Delivery Reduces The Risk Of Secondary Bleeding In Ischemic Stroke Rats, Maria Helen Harley Balch, Moner A. Ragas, Danny Wright, Kenny Reynolds, Bryce Kerr, Adrian M. Corbett

Neuroscience, Cell Biology & Physiology Faculty Publications

Background: Ongoing clinical trials are testing the effect of fluoxetine delivered post-stroke where a majority of patients are taking statins. This study determined the influence of the timing of administration of fluoxetine and statin on the final infarct volume and the risk of secondary bleeding in an animal model of ischemic stroke.

Methods and findings: Ischemic strokes were induced by endothelin-1 injection into two cortical sites of 10-12 month old female rats, targeting the forelimb motor cortex. Combined medications (5 mg/kg fluoxetine and 1 mg/kg simvastatin) were orally administered either beginning 6-12 hours or 20-26 hours after stroke induction and …

Neural Function, Injury, And Stroke Subtype Predict Treatment Gains After Stroke, Erin Burke Quinlan, Lucy Dodakian, Jill See, Alison Mackenzie, Vu Le, Mike Wojnowicz, Babak Shahbaba, Steven C. Cramer

Physical Therapy Faculty Articles and Research

Objective

This study was undertaken to better understand the high variability in response seen when treating human subjects with restorative therapies poststroke. Preclinical studies suggest that neural function, neural injury, and clinical status each influence treatment gains; therefore, the current study hypothesized that a multivariate approach incorporating these 3 measures would have the greatest predictive value.

Methods

Patients 3 to 6 months poststroke underwent a battery of assessments before receiving 3 weeks of standardized upper extremity robotic therapy. Candidate predictors included measures of brain injury (including to gray and white matter), neural function (cortical function and cortical connectivity), and clinical …