Neuroscience and Neurobiology Commons^™

Investigating The Role Of Neuronal Aging In Fragile X-Associated Tremor/Ataxia Syndrome, Katlin Marie Hencak

Honors Undergraduate Theses

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an X-linked late-onset neurodegenerative disorder caused by a noncoding trinucleotide repeat expansion in the FMR1 gene. This gene produces fragile x mental retardation protein (FMRP), an RNA binding protein whose targets are involved in brain development and synaptic plasticity. One of the proposed mechanisms of FXTAS pathogenesis is an RNA gain-of-function in which the repeat expansion causes toxic mRNA that sequesters important proteins in the cell, interfering with their functions. Another suggested method of pathogenesis is through a mutant protein called FMRpolyG. This protein results from repeat-associated non-AUG (RAN) translation, in which the expanded …

Molecular Basis Of Membrane Pore Formation By Amyloid Beta Peptide, Nabin Kandel

Electronic Theses and Dissertations

Alzheimer's Disease (AD) is a neurodegenerative disorder that affects around 50 million people worldwide and causes cognitive decline, brain atrophy and death. Despite extensive basic and clinical studies and drug development efforts, currently no effective treatments are available for AD. The amyloid β (Aβ) peptide is neurotoxic and is tightly associated with AD pathology, but the molecular mechanism of its action remains unclear. There are various forms of Aβ in the brain, ranging from the full length Aβ1-42 to shorter peptides, such as a strongly toxic Aβ25-35 fragment. The Amyloid Cascade Hypothesis (ACH) postulated that extracellular Aβ deposits cause the …

Rapid No• Measures In Rat Nucleus Accumbens And Frontal Cortex Following Nasal Administration Of Nitroglycerin, Victoria A. Scott

Theses and Dissertations--Medical Sciences

Nitric Oxide (NO) is a powerful endogenous free radical that has numerous biological functions including vasodilation and serves as a post synaptic second messenger in the central nervous system (CNS). Numerous studies implicate NO• involvement in CNS disorders such as schizophrenia and drug abuse. These studies address the direct in vivo determination of an FDA-approved NO• donor (nitroglycerin) on extracellular levels of NO• in the frontal cortex and core of the nucleus accumbens in a lightly anesthetized rat. State-of-the-art in vivo amperometric recording techniques coupled with a novel 4-channel low noise pre-amplifier system and new generation microelectrode arrays (MEAs) will …

Neuroprotective Strategies Following Experimental Traumatic Brain Injury: Lipid Peroxidation-Derived Aldehyde Scavenging And Inhibition Of Mitochondrial Permeability Transition, Jacqueline Renee Kulbe

Theses and Dissertations--Neuroscience

Traumatic brain injury (TBI) represents a significant health crisis. To date there are no FDA-approved pharmacotherapies available to prevent the neurologic deficits caused by TBI. Following TBI, dysfunctional mitochondria generate reactive oxygen and nitrogen species, initiating lipid peroxidation (LP) and the formation of LP-derived neurotoxic aldehydes, which bind mitochondrial proteins, exacerbating dysfunction and opening of the mitochondrial permeability pore (mPTP), resulting in extrusion of mitochondrial sequestered calcium into the cytosol, and initiating a downstream cascade of calpain activation, spectrin degradation, neurodegeneration and neurologic impairment.

As central mediators of the TBI secondary injury cascade, mitochondria and LP-derived neurotoxic aldehydes make promising …

Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford

Theses and Dissertations--Neuroscience

Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that …

The Role Of Endoplasmic Reticulum Stress In Ethanol-Induced Neurodegeneration, Yongchao Wang

Theses and Dissertations--Pharmacology and Nutritional Sciences

Heavy ethanol use causes neurodegeneration manifested by neuronal loss and dysfunction. It is becoming imperative to delineate the underlying mechanism to promote the treatment of ethanol-induced neurodegeneration. Endoplasmic reticulum (ER) stress is a hallmark and an underlying mechanism of many neurodegenerative diseases. This study aims to investigate the role of ER stress in ethanol-induced neurodegeneration. In experimental design, adult mice were exposed to binge ethanol drinking by daily gavage for 1, 5, or 10 days and the response of ER stress was examined. We found the induction of ER stress appeared at 5 days and remained at 10 days. Moreover, …

Exploring The Role Of Insulin Receptor Signaling In Hippocampal Learning And Memory, Neuronal Calcium Dysregulation, And Glucose Metabolism, Hilaree N. Frazier

Theses and Dissertations--Pharmacology and Nutritional Sciences

In the late 90’s, emerging evidence revealed that the brain is insulin-sensitive, highlighted by broad expression of brain-specific insulin receptors and reports of circulating brain insulin. Contemporary literature robustly supports the role of insulin signaling in normal brain function and suggests that insulin-related processes diminish with aging, evidenced by decreased signaling markers, reduced insulin receptor density, and lower levels of insulin transport across the blood-brain barrier. In the context of pathological cognitive decline, clinical trials using intranasal insulin delivery have reported positive outcomes on memory and learning in patients with mild cognitive decline or early-stage Alzheimer’s disease. However, while the …

The Rhesus Macaque Corticospinal Connectome, Sydney Talmi

CMC Senior Theses

The corticospinal tract (CST), which carries commands from the cerebral cortex to the spinal cord, is vital to fine motor control. Spinal cord injury (SCI) often damages CST axons, causing loss of motor function, most notably in the hands and legs. Our preliminary work in rats suggests that CST circuitry is complex: neurons whose axons project to the lower cervical spinal cord, which directly controls hand function, also send axon collaterals to other locations in the nervous system and may engage parallel motor systems. To inform research into repair of SCI, we therefore aimed to map the entire projection pattern, …

Identifying Dopamine Receptor Genes And Transcription Marbled Crayfish, Wolfgang Stein, Saisupritha Talasu

Faculty Publications – Biological Sciences

Modulatory transmitters are major contributors to nervous system plasticity and behavioral flexibility, they determine motivational states and are involved in psychiatric and neurological disorders. Neuromodulators act through a variety of distinct receptors and due to the diversity in receptor subtypes and distribution, a single neuromodulator can exert many different actions. A prerequisite to understand the ways modulators work is thus to identify which receptors are expressed in an animal.

I studied which Dopamine receptors are present in the Procambarus virginalis, a highly invasive species of all female genetic clones with high quality genome and transcriptomes. Their broad behavioral repertoire makes …

Relations Among Maternal And Paternal Behavior And Children's Stress Biology, S.K. Jiaming Lin, Stacey N. Doan, John Milton

Scripps Senior Theses

Parenting behavior has been shown to have a wide range of effects, influencing children’s psychological and biological stress outcomes. Most research focuses on maternal parenting behaviors, with few studies observing the effects of paternal behaviors or the influence of both parents on their children. In this study, the relationship between maternal and paternal parenting behaviors was examined in its association to predict children’s cortisol levels. Cultural differences in parenting styles was also observed. American (N=86) and Chinese (N=97) families participated in the study, with parents reporting their behaviors. Children’s cortisol was collected during a stressor task and correlational analysis was …

The Bionic Brain: Pragmatic Neuroethics And The Moral Plausibility Of Cognitive Enhancement, Peter A. Depergola Ii

Philosophy, Theology and Religious Studies Faculty Publications

The seemingly infinite possibilities of contemporary neuroscience span from the augmentation of memory, executive function, appetite, libido, sleep, and mood, to the maturation and development of emotional health and personality. These prospects hint at the capacity to alter neurocognitive conceptions of reality. They also mark the unavoidable inculcation of nuanced individual responses, perhaps radical, to these “tailor- made” perceptions. Hence, there exists certain neuroethical, and even more generally, existential risks within this fascinating and expeditious enterprise. The primary question in the context of present-day neurotechnology is not what can be done, but what should be. To that end, this paper …

Neural Processing Of Communication Signals: The Extent Of Sender–Receiver Matching Varies Across Species Of Apteronotus, Kathryne M. Allen, Gary Marsat

Faculty & Staff Scholarship

As communication signal properties change, through genetic drift or selective pressure, the sensory systems that receive these signals must also adapt to maintain sensitivity and adaptability in an array of contexts. Shedding light on this process helps us to understand how sensory codes are tailored to specific tasks. In a species of weakly electric fish, Apteronotus albifrons, we examined the unique neurophysiological properties that support the encoding of electrosensory communication signals that the animal encounters in social exchanges. We compare our findings to the known coding properties of the closely related species Apteronotus leptorhynchus to establish how these animals …

The Effect Of Mild Cognitive Impairment On Anxiety In Older Adults In American And Ukraine, Eleanor Ryan

Senior Honors Theses and Projects

With the growing population of elderly individuals throughout the world, the study of their emotional distress is ever poignant to society. This is especially true when these individuals have cognitive impairment. The research, in regards to Eastern European individuals, is lacking. To gain a better understanding of this understudied population, elderly people with Mild Cognitive impairment (MCI) from both Ukraine and the United States were studied. It was found that the anxiety rates of the Ukrainian MCI group were significantly higher than both the United States MCI group and the Ukraine control (p = 0.004). Purpose The purpose of this …

Targeting Maladaptive Plasticity After Spinal Cord Injury To Prevent The Development Of Autonomic Dysreflexia, Khalid C. Eldahan

Theses and Dissertations--Physiology

Vital autonomic and cardiovascular functions are susceptible to dysfunction after spinal cord injury (SCI), with cardiovascular dysregulation contributing to morbidity and mortality in the SCI population. Autonomic dysreflexia (AD) is a condition that develops after injury to the sixth thoracic spinal segment or higher and is characterized by potentially dangerous and volatile surges in arterial pressure often accompanied with irregular heart rate, headache, sweating, flushing of the skin, and nasal congestion. These symptoms occur in response to abnormal outflow of sympathetic activity from the decentralized spinal cord typically triggered by noxious, yet unperceived nociceptive stimulation beneath the level of lesion. …

Neural Circuits Underlying Rodent Sociality: A Comparative Approach, Nicole S. Lee, Annaliese K. Beery

Neuroscience: Faculty Publications

All mammals begin life in social groups, but for some species, social relationships persist and develop throughout the course of an individual’s life. Research in multiple rodent species provides evidence of relatively conserved circuitry underlying social behaviors and processes such as social recognition and memory, social reward, and social approach/avoidance. Species exhibiting different complex social behaviors and social systems (such as social monogamy or familiarity preferences) can be characterized in part by when and how they display specific social behaviors. Prairie and meadow voles are closely related species that exhibit similarly selective peer preferences but different mating systems, aiding direct …

Cross-Limb Dynamics Of Postural Tremor Due To Limb Loading To Fatigue: Neural Overflow But Not Coupling, Steven Morrison, Justin Kavanagh, Karl Newell

Rehabilitation Sciences Faculty Publications

Many experiments have shown independence of the index finger dynamics under bilateral postural tremor protocols. Here we investigated in young adults the dynamics of bilateral multidirectional postural tremor and forearm muscle activity under the progressively fatiguing conditions supporting an external weight to the point of induced postural failure. When no loads were applied, tremor in the vertical (VT) and mediolateral (ML) directions was similar with prominent peaks within 2- to 4-Hz and 8- to 12-Hz bandwidths. Contrastingly tremor in the anterior-posterior (AP) direction was characterized by a single peak between 0 and 2 Hz. Although no tremor coupling occurred cross …

Discrimination And Behavioral Responses To Communication Signals Compared Across Apteronotids., Danielle Leigh Dillon-Seeger

Graduate Theses, Dissertations, and Problem Reports (ETD)

Sensory systems are often uniquely tailored to encode behaviorally relevant signals and comparative studies across species can thus reveal how evolutionary changes shape sensory functions. The structure of communication signals varies widely between ghost knifefish species. Recent findings suggest that the nervous system co-adapted to the various signal structures observed across species to support different sensory behaviors. The aim for this thesis was to compare the sensory behavior of 3 species of ghost knifefish to contrast their behavioral performance with the known differences in neurophysiology. We hypothesize that for the different signal types and species, the ability to discriminate small …

Induction Of Cerebral Hyperexcitability By Peripheral Viral Challenge: Role Of Cxcl10 Chemokine, Tiffany J. Petrisko

Graduate Theses, Dissertations, and Problem Reports (ETD)

Peripheral viral infections are po­tent comorbid factors that exacerbate neuro­degene­ration. Although the under­lying mecha­nisms have not been defined, neuronal hyperexcitability has been established as an underlying feature. Our lab has developed a preclinical model in which a viral mimetic, poly­inosinic-poly­cytidylic acid (PIC) is injected in­tra­peritoneally to induce an anti-viral acute phase response (APR). APR in turn elicits robust neuronal hyperexcitability. The present study was undertaken to characterize molecular mechanisms that mediate the development of hyperexcitability in response to PIC challenge. The analysis of brain tissue after PIC challenge revealed a robust elevation of CXCL10 chemokine, indicating its putative role in …

Aptamer Functionalized Zinc Oxide Field Effect Transistors For Odor Detection, Michael D. Aldridge

Graduate Theses, Dissertations, and Problem Reports (ETD)

Odor detection and identification are complex processes, and tasks that currently only animals do well. There is a pressing need for an electronic nose, or eNose, with good sensitivity, selectivity, and speed that mimics that ability. Food quality control operations, environmental sensing, occupational safety, and the defense sectors all require systems that can rapidly and reliably detect trace levels of volatile organic compounds. The goal of this work is to create a biologically inspired device which can accurately detect and identify odors at concentrations consistent with the most sensitive biological systems.

In order to mimic a natural olfactory system, we …

Role Of Extracellular Vesicles In Neuroinflammatory Progression And Mitochondrial Functional Alterations, Ashley E. Russell

Graduate Theses, Dissertations, and Problem Reports (ETD)

Inflammation within the central nervous system (CNS), termed neuroinflammation, is a defining characteristic of many neuropathological conditions, including Alzheimer’s disease (AD) and stroke. Certain inflammatory mediators activate the transcription factor NF-κB, which induces transcription of many pro-inflammatory genes, including miR-34a and miR-146a. Several target candidate genes of these miRNAs encode for proteins of the mitochondrial electron transport chain. In our studies, we demonstrate that in response to inflammatory stimuli, such as TNF-α, the expression of miR-34a and -146a is significantly increased in several CNS cell types, and in their secreted extracellular vesicles (EVs). Exposure to TNF-α-derived EVs significantly increases cellular …