Life Sciences Commons^™

Brain Energy Homeostasis And The Regulation Of N-Acetyl-Aspartate Metabolism In Development And Disease, Samantha Zaroff

Graduate School of Biomedical Sciences Theses and Dissertations

N-acetylaspartate (NAA) is a non-invasive clinical marker of neuronal metabolic integrity because of its strong proton magnetic resonance spectroscopy (H-MRS) peak and direct correlation with energetic integrity. Specifically, NAA is used to track the progression of neurodegenerative diseases due to the characteristic reduction of whole brain levels of NAA which occur simultaneously with reduced glucose utilization and mitochondrial dysfunction, but prior to the onset of disease specific pathology. However, NAA will also significantly increase simultaneously with energetic integrity during periods of recovery or remission in applicable disorders, such as traumatic brain injuries. Unfortunately, it remains enigmatic exactly why NAA is …

Genetic Targeting And Anatomical Registration Of Neuronal Populations In The Zebrafish Brain With A New Set Of Bac Transgenic Tools, Dominique Förster, Irene Arnold-Ammer, Eva Laurell, Alison J. Barker, António M. Fernandes, Karin Finger-Baier, Alessandro Filosa, Thomas O. Helmbrecht, Yvonne Kölsch, Enrico Kühn, Estuardo Robles, Krasimir Slanchev, Tod R. Thiele, Herwig Baier, Fumi Kubo

Neuroscience: Faculty Publications

Genetic access to small, reproducible sets of neurons is key to an understanding of the functional wiring of the brain. Here we report the generation of a new Gal4- and Cre-driver resource for zebrafish neurobiology. Candidate genes, including cell type-specific transcription factors, neurotransmitter-synthesizing enzymes and neuropeptides, were selected according to their expression patterns in small and unique subsets of neurons from diverse brain regions. BAC recombineering, followed by Tol2 transgenesis, was used to generate driver lines that label neuronal populations in patterns that, to a large but variable extent, recapitulate the endogenous gene expression. We used image registration to characterize, …

Rescuing Age-Related Proteolysis Deficits With Methylene Blue, Shane E. Pullins

Theses and Dissertations

The average lifespan is constantly increasing with the advent of new medical techniques, and age-related cognitive decline is becoming a prevalent societal issue. Even during healthy aging, humans and rats exhibit progressive deficits in episodic/declarative memory. In laboratory rats, age-related memory impairment can be assessed with trace fear conditioning (TFC). Recent research implicates ubiquitin proteasome system-mediated protein degradation in the synaptic plasticity supporting memory formation and retrieval. In rats, aging leads to decreased basal proteolytic activity in brain structures known to support the acquisition and retrieval of trace fear memories, and our preliminary data suggests activity-dependent proteasome activity declines in …

A Neuroprotective Role For Mir-1017, A Non-Canonical Mirna, Matthew De Cruz

Master's Theses

miRNAs are post-transcriptional regulators of gene expression, with numerous being involved in neurobiology. Within the human genome a quarter of the identified miRNA loci derive from a class of miRNAs termed tailed mirtrons. Despite the identification of this large population of miRNA, no functional studies have been conducted to identify their role. In this study we examined the highly expressed and deeply conserved Drosophila 3’ tail mirtron, miR-1017, as a candidate to elucidate tailed mirtron functionality. We identified acetylcholine receptor transcripts, Da5 and Da2, as bona fide targets for miR-1017. Interestingly, Da2 is also the host transcript for miR-1017. We …

Circulating Autoantibodies In Human Traumatic Spinal Cord Injury Subjects And Their Relationship To The Development Of Neuropathic Pain, Georgene Hergenroeder

Dissertations & Theses (Open Access)

Background:

Approximately 17,500 spinal cord injuries (SCI) occur yearly in the U.S. causing considerable morbidity and mortality. Neuropathic pain (NP) ensues in 40-70% of SCI. An autoimmune response resulting from disruption of the blood-spinal cord-barrier may be a contributor to NP. However, the relationship between autoantibodies and NP after SCI in humans has not been thoroughly characterized nor have autoantigens been identified. Glial fibrillary acidic protein (GFAP) and collapsin response mediator protein2 (CRMP2) were identified as candidate autoantigens. The hypothesis is that proteins from the injured spinal cord released by SCI trigger autoantibody production which can lead to the development …

The Role Of Hippocampal And Medial Prefrontal Interactions In The Estrogenic Regulation Of Memory, Jennifer Tuscher

Theses and Dissertations

Dendritic spine plasticity is thought to be essential for the formation and storage of memories. The sex-steroid hormone 17-estradiol (E2) increases dendritic spine density in 2 brain regions necessary for memory formation, the dorsal hippocampus (DH) and medial prefrontal cortex (mPFC), but the mechanisms through which it does so remain largely unknown. Further, the extent to which these brain regions interact to mediate E2’s effects on memory is also unclear. Recently, we found that infusion of E2 directly into the DH also increases dendritic spine density in the DH and mPFC, and that these effects depend upon rapid activation of …

Complement 3a Receptor In Dorsal Horn Microglia Mediates Pronociceptive Neuropeptide Signaling, Suzanne Doolen, Jennifer Cook, Maureen Riedl, Kelley Kitto, Shinichi Kohsaka, Christopher N. Honda, Carolyn A. Fairbanks, Bradley K. Taylor, Lucy Vulchanova

Physiology Faculty Publications

The complement 3a receptor (C3aR1) participates in microglial signaling under pathological conditions and was recently shown to be activated by the neuropeptide TLQP‐21. We previously demonstrated that TLQP‐21 elicits hyperalgesia and contributes to nerve injury‐induced hypersensitivity through an unknown mechanism in the spinal cord. Here we determined that this mechanism requires C3aR1 and that microglia are the cellular target for TLQP‐21. We propose a novel neuroimmune signaling pathway involving TLQP‐21‐induced activation of microglial C3aR1 that then contributes to spinal neuroplasticity and neuropathic pain. This unique dual‐ligand activation of C3aR1 by a neuropeptide (TLQP‐21) and an immune mediator (C3a) represents a …

The Impact Of Delay On Retrieval Success In The Parietal Memory Network, Nathan Anderson

Arts & Sciences Electronic Theses and Dissertations

Recent work has identified a Parietal Memory Network (PMN), which exhibits regular patterns of activation during memory encoding and retrieval. Among these characteristic patterns, this network displays a strong “retrieval success” effect, showing greater activation for correctlyremembered studied items (hits) compared to correctly-rejected novel items (CRs). To date, most relevant studies have used short retention intervals. Here, we ask if the retrieval success effect seen in the PMN would remain consistent over a delay. Twenty participants underwent fMRI while encoding and recognizing scenes. Greater activity for hits than for correctly-rejected lures within PMN regions was observed after a short delay …

Endocytic Trafficking Of The Amyloid Precursor Protein In Rat Cortical Neurons, Sahily Reyes

Dissertations & Theses (Open Access)

Amyloid-beta (Aβ) aggregation and deposition into extracellular plaques is a hallmark of the most common forms of dementia, including Alzheimer’s disease. The Aβ-containing plaques result from pathogenic cleavage of amyloid precursor protein (APP) by secretases resulting in intracellular production of Aβ peptides that are secreted and accumulate extracellularly. Despite considerable progress towards understanding APP processing and Aβ aggregation, the mechanisms underlying endosomal production of Aβ peptides and their secretion remain unclear. Using endosomes isolated from cultured primary neurons, we determined that the trafficking of APP from the endosomal membrane into internal vesicles of late endosome/multivesicular bodies (MVB) is dependent on …

Preschoolers And Pandas Making Friends: A Journey About Healing From Brain Injury, Barbara Anne Doucette

Museum Studies Projects

Preschoolers that have obtained Non-Accidental Injury (NAI) from familial child abuse are in need of having a unique place for neurorehabilitation in correlation with traditional therapies. My thesis project suggests adding an exhibit annex to an existing giant panda exhibit that will give preschoolers an opportunity to help develop new neuropathways when exposed to mediation and creative activities. Meditation and creative activities are being examined by neuroscientists as an aid in neuroplasticity after brain injury. This thesis reviews the neurotypical preschooler’s milestones and the playful means by which they are achieved. Conjoining the contemporary museums’ and zoological gardens’ outreach to …

Mitochondrial Fission After Traumatic Brain Injury, Tara Fischer

Dissertations & Theses (Open Access)

Mitochondrial dysfunction is a central feature in the pathophysiology of Traumatic Brain Injury (TBI). Loss of mitochondrial function disrupts normal cellular processes in the brain, as well as impedes the ability for repair and recovery, creating a vicious cycle that perpetuates damage after injury. To maintain metabolic homeostasis and cellular health, mitochondria constantly undergo regulated processes of fusion and fission and functionally adapt to changes in the cellular environment. An imbalance of these processes can disrupt the ability for mitochondria to functionally meet the metabolic needs of the cell, therefore resulting in mitochondrial damage and eventual cell death. Excessive fission, …

Analytical Modeling Of A Communication Channel Based On Subthreshold Stimulation Of Neurobiological Networks, Alireza Khodaei

Department of Computer Science and Engineering: Dissertations, Theses, and Student Research

The emergence of wearable and implantable machines manufactured artificially or synthesized biologically opens up a new horizon for patient-centered health services such as medical treatment, health monitoring, and rehabilitation with minimized costs and maximized popularity when provided remotely via the Internet. In particular, a swarm of machines at the scale of a single cell down to the nanoscale can be deployed in the body by the non-invasive or minimally invasive operation (e.g., swallowing and injection respectively) to perform various tasks. However, an individual machine is only able to perform basic tasks so it needs to exchange data with the others …

Exercise, Learning And Emotional Health: Interdisciplinary Approaches To Translational Action, Tessa L. Koschel

UNLV Theses, Dissertations, Professional Papers, and Capstones

Exercise positively effects physical, psychological and neurological wellbeing. Though the population at large is becoming increasingly aware of the multi-faceted benefits of exercise, the majority of people fail to meet daily exercise recommendations. Largely, demands of everyday life such as work, school and family take priority over fitness. The issue therefore becomes a matter of time. In a world of media multi-tasking and immediate gratification, the challenge to health professionals becomes incorporation and manipulation of these consistencies to improve exercise uptake and adherence. Focus must shift from the idea of making additional time for exercise, to adding exercise to time …

Binge Alcohol Exposure Transiently Changes The Endocannabinoid System: A Potential Target To Prevent Alcohol-Induced Neurodegeneration, Daniel J. Liput, James R. Pauly, Audra L. Stinchcomb, Kimberly Nixon

Pharmaceutical Sciences Faculty Publications

Excessive alcohol consumption leads to neurodegeneration, which contributes to cognitive decline that is associated with alcohol use disorders (AUDs). The endocannabinoid system has been implicated in the development of AUDs, but little is known about how the neurotoxic effects of alcohol impact the endocannabinoid system. Therefore, the current study investigated the effects of neurotoxic, binge-like alcohol exposure on components of the endocannabinoid system and related N-acylethanolamines (NAEs), and then evaluated the efficacy of fatty acid amide hydrolase (FAAH) inhibition on attenuating alcohol-induced neurodegeneration. Male rats were administered alcohol according to a binge model, which resulted in a transient decrease in …

Characterizing Mekk1: Candidate Behavioural Isolation Gene, Caryn Dooner

Electronic Thesis and Dissertation Repository

Behavioural isolation can occur due to divergence in aspects of courtship and mating, and can contribute to reproductive isolation. The purpose of this study is to determine how a gene, Mekk1, contributes to female rejection behaviour between D. melanogaster and D. simulans. Unique polymorphisms were identified within D. simulans Mekk1 that could contribute to behaviour, most of which are non-coding. Both transcripts of Mekk1 appear to be expressed at similar levels in D. simulans and D. melanogaster. These data also indicate that Mekk1 may be expressed in a specific region of the brain called the mushroom body, …

Feature-Based Learning Improves Adaptability Without Compromising Precision, Shiva Farashahi, Katherine Rowe, Zohra Aslami, Daeyeol Lee, Alireza Soltani

Dartmouth Scholarship

Learning from reward feedback is essential for survival but can become extremely challenging with myriad choice options. Here, we propose that learning reward values of individual features can provide a heuristic for estimating reward values of choice options in dynamic, multi-dimensional environments. We hypothesize that this feature-based learning occurs not just because it can reduce dimensionality, but more importantly because it can increase adaptability without compromising precision of learning. We experimentally test this hypothesis and find that in dynamic environments, human subjects adopt feature-based learning even when this approach does not reduce dimensionality. Even in static, low-dimensional environments, subjects initially …

Temperature Effects On An Axon’S Ability To Maintain Phasing Of A Rhythmic Motor System, Marissa Elaine Cruz

Theses and Dissertations

The precise timing of action potentials generated in the nervous system is crucial for generating adequate behavior. Once generated, action potentials travel along axons towards the neurons or muscles they innervate. Axons are also responsible for preserving the temporal fidelity of the generated action potentials. One challenge axons face is that they can be of considerable length, and exposed to changes in internal and external conditions. Temperature fluctuations, for example, affect the ion channels that generate and propagate action potentials causing changes in action potential speed. It is unclear if, and how, the timing of action potentials can be preserved …

Glutamylation Regulates Transport, Specializes Function, And Sculpts The Structure Of Cilia, Robert O'Hagan, Malan Silva, Ken Cq Nguyen, Winnie Zhang, Sebastian Bellotti, Yasmin Ramadan, David Hall, Maureen M. Barr

Department of Biology Faculty Scholarship and Creative Works

Ciliary microtubules (MTs) are extensively decorated with post-translational modifications (PTMs), such as glutamylation of tubulin tails. PTMs and tubulin isotype diversity act as a “Tubulin Code” that regulates cytoskeletal stability and the activity of MT-associated proteins such as kinesins. We previously showed that, in C. elegans cilia, the deglutamylase CCPP-1 affects ciliary ultrastructure, localization of the TRP channel PKD-2 and the kinesin-3 KLP-6, and velocity of kinesin-2 OSM-3/KIF17, while a cell-specific α-tubulin isotype regulates ciliary ultrastructure, intraflagellar transport, and ciliary functions of extracellular vesicle (EV)-releasing neurons. Here, we examine the role of PTMs and the Tubulin Code in the cililary …

Novel Calcium-Related Targets Of Insulin In Hippocampal Neurons, Shaniya Maimaiti, Hilaree N. Frazier, Katie L. Anderson, Adam O. Ghoweri, Lawrence D. Brewer, Nada M. Porter, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

Both insulin signaling disruption and Ca²⁺ dysregulation are closely related to memory loss during aging and increase the vulnerability to Alzheimer's disease (AD). In hippocampal neurons, aging-related changes in calcium regulatory pathways have been shown to lead to higher intracellular calcium levels and an increase in the Ca²⁺-dependent afterhyperpolarization (AHP), which is associated with cognitive decline. Recent studies suggest that insulin reduces the Ca²⁺-dependent AHP. Given the sensitivity of neurons to insulin and evidence that brain insulin signaling is reduced with age, insulin-mediated alterations in calcium homeostasis may underlie the beneficial actions of insulin in …

Oculomotor Executive Dysfunction During The Early And Later Stages Of Sport-Related Concussion Recovery, Brandon Webb

Electronic Thesis and Dissertation Repository

Executive dysfunction represents a persistent concussion deficit; however, it is largely unclear whether the deficit persists in an athlete after they have been deemed safe to return to play. In the present work, athletes with a sport-related concussion, and their age- and sex-matched controls, completed prosaccades and executive-related antisaccades: (1) 2-6 days post-concussion (i.e., initial assessment), and (2) 14-20 days after initial assessment and only when an athlete was medically cleared for safe return to play (i.e., follow-up assessment). Initial assessment antisaccades for the concussed group produced longer reaction times (RT) and more directional errors than the control group. The …

Jennifer Maurer Phd Thesis.Pdf, Jennifer Maurer

Jennifer Maurer

P2x2 Dominant Deafness Mutations Have No Negative Effect On Wild-Type Isoform: Implications For Functional Rescue And In Deafness Mechanism, Yan Zhu, Juline Beudez, Ning Yu, Thomas Grutter, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

The P2X2 receptor is an ATP-gated ion channel, assembled by three subunits. Recently, it has been found that heterozygous mutations of P2X2 V60L and G353R can cause autosomal dominant nonsyndromic hearing loss. However, the underlying mechanism remains unclear. The fact that heterozygous mutations cause deafness suggests that the mutations may have dominant-negative effect (DNE) on wild-type (WT) P2X2 isoforms and/or other partners leading to hearing loss. In this study, the effect of these dominant deafness P2X2 mutations on WT P2X2 was investigated. We found that sole transfection of both V60L and G353R deafness mutants could efficiently target to the plasma …

Modeling Aggregation Of Proliferating Microglia In Response To Amyloid-Beta In Dementia, Adrienne C. Kinney, Ellen R. Swanson

Spora: A Journal of Biomathematics

Amyloid-beta plaques are prominent biological markers in dementia brains. In response to plaque formation, the brain's immune cells, microglia, become reactive. Microglia are measurable cells that surround amyloid-beta plaques, indicating their location. A system of partial differential equations describes the concentration of microglia in dementia brains by incorporating chemotactic signaling. However, this system fails to incorporate increasing numbers of reactive microglia cells in response to amyloid-beta aggregation. A system of ordinary differential equations describing the number of significant cells and proteins in the brain suggests the amount of reactive microglia increases significantly during the progression of dementia. We couple these …

Low Arousal Positive Emotional Stimuli Attenuate Aberrant Working Memory Processing In Persons With Mild Cognitive Impairment, Lucas S. Broster, Shonna L. Jenkins, Sarah D. Holmes, Gregory A. Jicha, Yang Jiang

Behavioral Science Faculty Publications

Emotional enhancement effects on memory have been reported to mitigate the pathophysiology of Alzheimer’s disease (AD). However, relative to their manifestation in persons without pathologic aging, these effects may be reduced in magnitude or even deleterious, especially in tasks that more closely model ecologic memory performance. Based upon a synthesis of such reports, we hypothesized that in persons with AD low arousal positive stimuli would evoke relatively intact emotional enhancement effects, but that high arousal negative stimuli would evoke disordered emotional enhancement effects. To assess this, participants with and without mild cognitive impairment (MCI) presumed to be due to AD …

Language Experience With A Native-Language Phoneme Sequence Modulates The Effects Of Attention On Cortical Sensory Processing, Valerie L. Shafer, Monica Wagner, Jungmee Lee, Francesca Mingino, Colleen O'Brien, Adam Constantine, Mitchell Steinschneider

Publications and Research

Auditory evoked potentials (AEP) reflect spectro-temporal feature changes within the spoken word and are sufficiently reliable to probe deficits in auditory processing. The current research assessed whether attentional modulation would alter the morphology of these AEPs and whether native-language experience with phoneme sequences would influence the effects of attention. Native-English and native-Polish adults listened to nonsense word pairs that contained the phoneme sequence onsets /st/, /sət/, /pət/ that occur in both the Polish and English languages and the phoneme sequence onset /pt/ that occurs in the Polish language, but not the English language. Participants listened to word pairs within two …

Neuronal Degeneration And Short-Term Memory Impairment After Tbi, Obiamaraije Igwe

Posters-at-the-Capitol

Traumatic brain injury (TBI) was associated with impaired short-term memory with causes of vehicle accidents and falls. Protein plaques containing fibrinogen (Fg), are associated with memory loss. After TBI, Fg in blood was higher than normal (>~2 mg/ml), which resulted in increased Fg in extravascular space. Therefore, Fg bonded to its endothelial receptor intercellular adhesion molecule-1 (ICAM-1). Fg then interacted with cellular prion protein (PrPC), which had a strong effect on the loss of memory and cognition. Mechanisms of Fg and PrPC complex formation and its functional implication are not known. This present study tested the level of Fg-PrPC …

Sex Differences In Estradiol Signaling In The Zebra Finch (Taeniopygia Gutatta) Auditory Cortex, Amanda Krentzel

Doctoral Dissertations

Although several sex differences have been described in brain structure, function, and development, sex as a biological factor is underrepresented in neuroscience studies. In the mammalian brain, there are sex differences in the mechanism of rapid estradiol actions on neuronal physiology. In the songbird, the brain is a major source of estradiol production, and estradiol rapidly modulates auditory responsiveness through dynamic changes and an unknown receptor mechanism. I set out to determine if there are sex differences in rapid estradiol modulation of auditory cortical activity, as has been shown in other systems. I tested this hypothesis through three aims: 1) …

The Role Of Sleep On Inhibitory Control In Young Children With Attention-Deficit/Hyperactivity Disorder (Adhd), Amanda Cremone

Doctoral Dissertations

Alongside the hallmark symptoms of hyperactivity and inattention, children with attention-deficit/hyperactivity disorder (ADHD) often report having sleep problems. Although sleep deficits are consistently found when evaluated subjectively, impairments in sleep physiology are inconsistent. Compared to typically developing (TD) children, children with ADHD have greater spectral power in the delta (0.5 to 4 Hz) and theta frequency bands (4 to 7 Hz). Moreover, activity in these bands is differentially related to cognitive outcomes in ADHD and TD populations. As such, this dissertation sought to examine relations between sleep physiology and inhibitory control, a primary deficit of ADHD, in young children with …

Brain Wellness: Team Leaders And Steering Committee, University Of Mississippi. Brain Wellness Constellation

Brain Wellness

No abstract provided.

Dynamic Range Of Frontoparietal Functional Modulation Is Associated With Working Memory Capacity Limitations In Older Adults, Jonathan G. Hakun, Nathan F. Johnson

Physical Therapy Faculty Publications

Older adults tend to over-activate regions throughout frontoparietal cortices and exhibit a reduced range of functional modulation during WM task performance compared to younger adults. While recent evidence suggests that reduced functional modulation is associated with poorer task performance, it remains unclear whether reduced range of modulation is indicative of general WM capacity-limitations. In the current study, we examined whether the range of functional modulation observed over multiple levels of WM task difficulty (N-Back) predicts in-scanner task performance and out-of-scanner psychometric estimates of WM capacity. Within our sample (60–77 years of age), age was negatively associated with frontoparietal modulation range. …