Medicine and Health Sciences Commons^™

Investigating The Role Of Endogenous Atf4 Upregulation On Neuronal Glutathione Level, Fatemeh Mirshafiei

Electronic Thesis and Dissertation Repository

ATF4 is a transcription factor that is activated in response to integrated stress response (ISR). In neurons specifically, ATF4 has been suggested to act as a pro-apoptotic transcription factor. The expression of ATF4, as well as its downstream gene targets have been implicated in both in vivo and in vitro models of Alzheimer’s and Parkinson’s Disease. However, the mechanism by which ATF4 promotes cell death remains unclear. It was previously shown that overexpression of ATF4 in primary cortical neurons caused a reduction in glutathione levels, resulting in oxidative stress-induced cell death. The aim of this project was to investigate whether …

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 …

Medial Geniculate Projections To Auditory And Visual Cortex In Hearing And Deaf Cats, Benjamin Trachtenberg

Electronic Thesis and Dissertation Repository

Following early-onset deafness, studies have demonstrated crossmodal plasticity, throughout “deaf” auditory cortex. Crossmodally reorganized auditory cortex shows increased dendritic spine density, which suggests increased numbers of axon terminals. I examined projections from the medial geniculate body (MGB) of hearing and early-deaf cats in order to reveal the distribution of synaptic boutons in the cortex, originating from MGB neurons. Anterograde fluorescent dextran tracers were deposited bilaterally in the MGB in order to label cortical axon terminals. Deafness resulted in axon terminal increases in visual cortex, and conservation of auditory axon terminal distribution. Visual areas PLLS and area 18 received increased projections …

Cyclophilin 40 As A Novel Disaggregase, Jeremy Dustin Baker

USF Tampa Graduate Theses and Dissertations

The negative health and economic impacts of neurodegenerative diseases on Americans is astounding and accelerating with an aging population. The Alzheimer’s Association reports that 5.7 million Americans suffer from Alzheimer’s disease (AD), a number which is expected to increase to 14 million by 2050. In economic terms, AD and other neurodegenerative disorders will cost the US over $275 billion in 2018, rising to over $1 trillion annually by 2050. AD causes gross brain atrophy and is most damaging throughout the cortex and the hippocampus, regions required for higher cognitive function and memory. AD presents as tangles within neurons composed of …

Proteolysis Of Cx3cl1 Impacts Cx3cr1 Signaling And Therapeutic Benefits In A Tauopathy Model, Dylan John Finneran

USF Tampa Graduate Theses and Dissertations

Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder and the most common form of dementia. The hallmark pathologies of AD are extracellular aggregates of amyloid-beta, intracellular aggregates of microtubule associated protein tau and increased neuroinflammation. Current therapeutics offer only symptomatic relief and clinical trials investigating therapeutic benefits of non-steroidal anti-inflammatory drugs have yielded no positive results. Therefore, recent work has focused on immunomodulators, such as CD200 and fractalkine, as potential therapeutic targets for AD.

Fractalkine (CX3CL1; FKN) is expressed as a transmembrane protein with an N-terminal chemokine domain followed by a long, mucin-like stalk. FKN can signal as a membrane-bound …

White Matter Inflammation And Executive Dysfunction: Implications For Alzheimer Disease And Vascular Cognitive Impairment, Alexander Levit

Electronic Thesis and Dissertation Repository

White matter integrity is crucial to healthy executive function, the cognitive domain that enables functional independence. However, in the ageing brain, white matter is highly vulnerable. White matter inflammation increases with age and Alzheimer disease (AD), which disrupts the normal function of white matter. This may contribute to executive dysfunction, but the relationship between white matter inflammation and executive function has not been directly evaluated in ageing nor AD. White matter is also particularly vulnerable to cerebrovascular disease, corresponding with the common presentation of executive dysfunction in vascular cognitive impairment (VCI). Thus, white matter may be an important substrate by …

Demonstration Of Monolithic-Silicon Carbide (Sic) Neural Devices, Evans K. Bernardin

USF Tampa Graduate Theses and Dissertations

Brain Machine Interfaces (BMI) provide a communication pathway between the electrical conducting units of the brain (neurons) and external devices. BMI technology may provide improved neurological and physiological functions to patients suffering from disabilities due to damaged nervous systems. Unfortunately, microelectrodes used in Intracortical Neural Interfaces (INI), a subset of the BMI device family, have yet to demonstrate long-term in vivo performance due to material, mechanical and electrical failures. Many state-of-the-art INI devices are constructed using stacks of multiple materials, such as silicon (Si), titanium (Ti), platinum (Pt), parylene C, and polyimide. Not only must each material tolerate the biological …

Limbic System Involvement In Absence Seizures, Rukham Ajaz

Electronic Thesis and Dissertation Repository

Absence epilepsy is characterized by brief spells of absent stare and spike wave discharges (SWDs), generally believed to be generated by a thalamocortical network. Our lab showed that hippocampal neuronal firings were synchronous with SWDs in a gamma butyrolactone (GBL) model of absence epilepsy in rats (Arcaro et al., 2016). We hypothesize that, in a GBL model of absence seizures, 30-400 Hz oscillations in the spontaneous local field potentials (LFPs) in the hippocampus and other parts of limbic system (amygdala and nucleus accumbens) are phase modulated by SWDs, and this modulation is mediated through nucleus reuniens of midline thalamus (RE). …

Pathogenicity And Protection Mediated By A Single Tcrβ In Experimental Autoimmune Encephalomyelitis, Tianhua Wu

Theses and Dissertations (ETD)

How the TCR repertoire, together with risk-associated major histocompatibility complex (MHC), imposes susceptibility for autoimmune disease is not fully understood. A small fraction of TCR α or β chains are “public”, and are shared by most individuals.High-throughput sequencing of the mouse TCRβ repertoire during myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmuneencephalomyelitis (EAE) identified a public TCRβ chain, TCRβ1, which was highly shared among individual mice and preferentially deployed during EAE. Retrogenic expression of TCRβ1 resulted in spontaneous early-onset EAE in mice with high penetrance and severity, despite being paired with a diverse endogenous TCRα repertoire. To further study autoimmunity conferred by …

Resting-State Functional Connectivity In Youth With Gender Dysphoria, Felix L. Garcia

Dissertations, Theses, and Capstone Projects

Current developmental models of gender identity and gender dysphoria (GD) lack sex-specific profiles of brain function that differentiate between typically-developing and cross-gender identified youth, as postulated by models like the unified theory of the origins of sex differences (Arnold, 2009) and the neurobiological theory of the origins of transsexuality (Swaab & Garcia-Falgueras, 2009). Previously, investigators have used brain imaging modalities such as Resting-State functional Magnetic Resonance Imaging (R-fMRI) to demonstrate differences in resting-state functional connectivity (RSFC) between typically-developing male and female youth, and between typically-developing and GID-diagnosed youth. In the present pilot study, I used R-fMRI to investigate differences in …

Neuroprotective Functions Of Docosahexaenoic Acid And Epidermal Fatty Acid Binding Protein, Manuel Luis Montero

Loma Linda University Electronic Theses, Dissertations & Projects

Lipotoxicity (LTx) is involved in mostly every process of neuronal injury. Using NGFDPC12 cells we show that palmitic acid (PA) induces the expression of stress response genes HIF-1α and BNIP3, increases the accumulation of reactive oxygen species, and decreases cell viability by apoptosis. Inhibition of cathepsins does not rescue neurons from PA-LTx but inhibition of necroptosis and promotion of autophagy do. DHA decreases the expression of HIF-1α and BNIP3 and rescues PA-induced cell death by inhibiting apoptosis and necroptosis. Besides DHA stimulates the mRNA expression, phosphorylation and conjugation of autophagy controlling proteins. Inhibiting autophagy during DHA treatment decreases its capacity …

Integrative Signaling Of Mitochondria, Trpa1 And Trpv1 In Vagal Neurons, Katherine Stanford

USF Tampa Graduate Theses and Dissertations

Sensory nerves detect conditions in the external and internal environment and permit behavioral and physiological responses to maintain homeostasis and ensure survival. As such, sensory nerves detect a wide variety of stimuli including heat, touch, pH, and vibration. The precise nature of these responses is dependent upon the initiating stimulus and site of activation. Potentially threatening stimuli (noxious heat, cellular damage, chemical irritants) activate nociceptive sensory nerves through the gating of ion channels expressed at sensory nerve terminals, thereby evoking defensive reflexes such as cough, watering eyes and limb withdrawal as well as sensations of pain or discomfort. While these …

Properties Of Synaptic Transmission From Rods And Cones In The Outer Plexiform Layer Of The Vertebrate Retina, Xiangyi Wen

Theses & Dissertations

Photoreceptors are the first neurons in the visual system. They transduce changes in light intensity into graded changes in membrane potential that are then transformed into chemical signals by regulating the release of glutamate-filled synaptic vesicles. Rod and cone photoreceptors release glutamate continuously in darkness and release slows in light. To help track rapid changes in light intensity, photoreceptors are capable of both rapid exocytosis and rapid endocytosis of synaptic vesicles.

Endocytosis is needed for recycling synaptic vesicles but also appears to be important for removing proteins and lipids from active zones to restore release site function after prior vesicle …

An Interface Of The Taste And Reward Systems In The Brainstem And Its Role In Feeding, Louis Saites

Theses and Dissertations (ETD)

We eat what tastes good. We also eat because it is necessary for our health. In fact, some of the most nutritious foods (e.g., vegetables) are often less appetizing, and the tastiest (e.g., fast food, ice cream) may be the least healthy. Despite the former, we may also have a lower limit of what we accept at which point nutrition becomes irrelevant (e.g., “spinach is just too yucky”). Further, we may eat unhealthily because of overwhelming urges. We investigated the complex interactions of taste and feeding at the neurobiological level using the experiments described.

In one sense, this neurobiology begins …

An Evaluation Of Alzheimer's Disease-Related Pathology In Two Different Models Of Diabetes In Immune-Challenged Mice, Andrew Scott Murtishaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome are related disorders with wide-ranging and devastating effects that can be observed throughout the body. One important and understudied organ of damage is the brain. Clinical and epidemiological studies have found that T2DM, and more specifically hyperinsulinemia, significantly increases the risk of cognitive decline and increases the likelihood of Alzheimer’s disease (AD) and other forms of dementia in the elderly. Insulin has slightly different functions in the peripheral body than in the central nervous system and the dysregulation of these functions may contribute to the onset and progression of late-life neurodegenerative …

Brazilian Jiu Jitsu: A Tool For Veteran Reassimilation, Gino L. Collura

USF Tampa Graduate Theses and Dissertations

This dissertation evaluates veteran participation in the martial art of Brazilian Jiu Jitsu (BJJ) as a tool of reassimilation for veterans suffering from anxiety, stress and/or combat PTSD associated with military deployment. From the onset of Operation Iraqi Freedom, Operation Enduring Freedom and Operation New Dawn, challenges associated with U.S. Veteran assimilation and reintegration have been increasing. Coping with long term displacement, trauma, loss, and making sense of identity shifts between being an active duty service member and civilian can often present challenges when navigating back into civilian life.

By utilizing a neuroanthropological lens, ethnographic inquiry, surveys, semi-structured interviews, and …

Effects Of Mild Traumatic Brain Injury On Ethanol Consumption And The Combined Effects On Neuroinflammation, Cognition, And Behavior In Mice, Jessica L. Hoffman

USF Tampa Graduate Theses and Dissertations

The relationship between alcohol consumption and traumatic brain injury (TBI) often focuses on alcohol consumption increasing the likelihood of incurring a TBI, rather than alcohol use outcomes after TBI. This focus is in part due to the large numbers of TBI patients visiting emergency rooms notable levels of alcohol in their blood. Additionally, increases in alcohol use disorders following TBI can be predicted by previous history of alcohol use. However, studies have also shown patients without a history of an alcohol use disorder can experience increases in problem drinking after single or multiple TBIs. Due to the diffuse impact of …

Testing The Efficacy Of Transcranial Magnetic Stimulation (Tms) In Treating Depression In Patients With Cognitive Impairment, Daniel Robert Schaffer

Psychology Theses & Dissertations

The purpose of this study is to (1) examine the efficacy of Transcranial Magnetic Stimulation (TMS) in treating depression among individuals with cognitive impairment and (2) to examine if TMS is capable of facilitating cognitive improvements independent of mood improvements. Mild cognitive impairment (MCI) is often seen as a pre-clinical stage to dementia, and depressive disorders are highly prevalent among both MCI and dementia. There is a large body of research that has linked depressive disorders as a prodromal symptom of MCI and the later development of dementia. While some researchers debate whether or not this link between depression and …

Developmental Steps For A Functional Three-Dimensional Cell Culture System For The Study Of Asymmetrical Division Of Neural Stem Cells, Martina Zamponi

Biomedical Engineering Theses & Dissertations

Stem cells are a cell type present during and following development, which possess self- renewal properties, as well as the ability to differentiate into specific cells. Asymmetrical division is the cellular process that allows stem cells to produce one differentiated and one un-differentiated daughter cell during the same mitotic event. Insights in the molecular mechanisms of such process are minimal, due to the absence of effective methods for its targeted study. Currently, traditional methods of investigation include monolayer cell culture and animal models. The first poses structural limitations to the accurate representation of human tissue and cell structures, while animal …

Therapeutic Modulation Of Alzheimer’S Disease With Biological (Hucbs) And Pharmacological (Lispro) Approaches, Md Ahsan Habib

USF Tampa Graduate Theses and Dissertations

Dementia is the top global public health threat of the twenty first century. Within the dementia spectrum, Alzheimer’s disease (AD) is the most common type of dementia that occurs with aging and accounts for about 60% - 80% of diagnosed cases. But currently available discoveries failed to develop disease-modifying therapies for all patients living with AD. Recent discoveries can only partially slow down cognitive decline in a small subset of patients with limited effectiveness. The heterogeneity and complexity of the pathophysiology of AD indicate that a single drug approach may not be sufficient to prevent disease onset and progression. Human …

A Normalization Circuit Of Attention In Primate Lateral Prefrontal Cortex, Lyndon Duong

Electronic Thesis and Dissertation Repository

The way in which visual neurons encode information pertaining to a cluttered scene with multiple stimuli, and subsequently filter behaviorally relevant information using attention remains poorly understood. Neurons of area 8a in the macaque lateral prefrontal cortex have been shown to encode visual and attentional signals. We trained two macaque monkeys in a visuospatial attention task and performed neurophysiological recordings to test how neurons in this area encode multiply presented stimuli and attentionally filter target stimuli from distractors. We found area 8a neuronal responses to several concurrently presented stimuli to resemble the average of individual responses to those stimuli when …

Pip2 Modulation Of Afterhyperpolarizations In Magnocellular Supraoptic Neurons, Matthew Karl Kirchner

Theses and Dissertations (ETD)

Magnocellular neurosecretory cells (MNCs) are large oxytocin (OT)- and vasopressin (VP)-releasing neurons that secrete these hormones into the circulatory system in response to physiological stimuli. These cells exhibit unique phasic and burst firing patterns to release these peptides into the circulatory system where they primarily control milk ejection and parturition (OT) as well as salt-water balance and vasoconstriction (VP). This firing is underlain by intrinsic ionic mechanisms that shape the duration and frequency of these bursts. One of these mechanisms is the Ca2+-dependent afterhyperpolarization (AHP), which activates during bursts and causes spike frequency adaptation. This afterhyperpolarization has three distinct conductances: …

Defining The Radioresponse Of Mossy Cells, Devon Ivy

Electronic Theses, Projects, and Dissertations

Clinical radiotherapy is used to treat a variety of brain tumors within the central nervous system. While effective, it can result in progressive and debilitating cognitive impairment that can diminish quality of life. These impairments have been linked to hippocampal dysfunction and corresponding deficits in spatial learning and memory. Mossy cells are a major population of excitatory neurons located within the dentate hilus and highly involved in hippocampal circuitry. They play critical roles in spatial navigation, neurogenesis, memory, and are particularly vulnerable to a variety of neurotoxic insults. However, their sensitivity to ionizing radiation has yet to be investigated in …

Submandibular Mechanical Stimulation Of Upper Airway Muscles To Treat Obstructive Sleep Apnea, Ferhat Erdogan

Dissertations

The extrinsic tongue muscles are activated in coordination with pharyngeal muscles to keep a patent airway during respiration in wakefulness and sleep. The activity of genioglossus, the primary tongue-protruding muscle playing an important role in this coordination, is known to be modulated by several reflex pathways mediated through the mechanoreceptors of the upper airways. The main objective is to investigate the effectiveness of activating these reflex pathways with mechanical stimulations, for the long-term goal of improving the upper airway patency during disordered breathing in sleep. The genioglossus response is examined during mandibular and sub-mandibular mechanical stimulations in healthy subjects during …

Electrophysiological Biomarkers Of Chemotherapy-Related Cognitive Impairment In Hematological Malignancy Patients, David E. Anderson

Theses & Dissertations

Multiple cancer populations frequently report cognitive impairment following treatment with chemotherapy agents (“chemo-brain”). Impaired neuropsychological performance is commonly reported in cognitive domains of attention and executive function. Understanding neural mechanisms underlying cognitive impairments is essential to developing prevention and rehabilitation strategies. Brain imaging studies frequently show chemotherapy-related impairments within the attentional control network, which is comprised of a constellation of cortical regions that govern reportedly impaired cognitive functions. In the current dissertation research, I developed a novel electrophysiology battery aimed at recording near-instantaneous neural activity within the attentional control network during cognitive task performance. Cancer patients diagnosed with hematological malignancy …

Behavior Coding Strategies: Population Coupling And The Functional Role Of Excitatory/Inhibitory Balance In Primary Motor Cortex, Patrick Aaron Kells

Graduate Theses and Dissertations

The complexities of an organism’s experience of- and interaction with the world are emergent phenomena produced by large populations of neurons within the cerebral cortex and other brain regions. The network dynamics of these populations have been shown to be sometimes synchronous, with many neurons firing together, and sometimes asynchronous, with neurons firing more independently, leading to a decades-old debate within the neuroscience community. This discrepancy comes from viewing the system at two different scales; at the single cell level, the spiking activity of two neurons within cortex tend to be rather independent, but when the average activity of a …

Transcranial Direct Current Stimulation (Tdcs) Improves Performance On Spelling And Word Detection Tasks, J. Kevin Wilson

Psychology ETDs

Deficits in written language involving spelling can have negative effects on a person’s education and occupation. Conventional spelling therapy is a time consuming and cost-prohibitive option, if even available, highlighting the need for improved methods for remediation. One possible way to address this need may be through the use of transcranial direct current stimulation (tDCS). This study sought to examine the effects of tDCS on performance during spelling, word detection, and facial recognition tasks. Active or sham tDCS was randomly assigned to typically functioning adults. The anode electrode was placed over Broca’s area (F7 in the 10/20 EEG system) and …

Targeting The Hsp90/Aha1 Complex For The Treatment Of Tauopathies, Lindsey Brooke Shelton

USF Tampa Graduate Theses and Dissertations

The microtubule associated protein, tau, is involved in regulating microtubule stability and axonal transport. When tau becomes hyperphosphorylated it can disassociate from the microtubules and start to aggregate. These tau aggregates are the hallmarks of many diseases known as tauopathies. The heat shock protein 90 kDa (Hsp90) chaperone network is highly involved in modulating client proteins, including tau. However, during aging and disease the Hsp90 chaperone network becomes highly imbalanced with some Hsp90/co-chaperone complexes increasing, while others are repressed. This imbalance in Hsp90/co-chaperone complexes could result in a worsening of tau pathology in Alzheimer’s disease.

Hsp90 inhibition has been of …

Neural Mechanisms Of Transcranial Magnetic Stimulation In The Treatment Of Tinnitus, Andrea S. Lowe

USF Tampa Graduate Theses and Dissertations

Millions of people suffer from tinnitus, a disorder for which there is currently no effective treatment or cure. My dissertation work provides insight into the neural correlates of this pervasive hearing disorder and examines how a newly emerging therapy, transcranial magnetic stimulation (TMS), affects the central auditory system in the generation of the tinnitus percept. This work has a multifold focus of: i) developing and modeling the function of a miniature magnetic coil that can be used for TMS in rodents, ii) establishing a reliable mouse model of tinnitus that can be used for assessing TMS treatment-induced changes, iii) measuring …

Examining The Role Of Ganglioside Homeostasis In Neurodegeneration And Aging Using Maldi Imaging Mass Spectrometry, Sarah Caughlin

Electronic Thesis and Dissertation Repository

Gangliosides are a family of membrane lipids enriched in the central nervous system (CNS) that play an important role in cell signaling processes on the membrane. Alterations in the homeostatic distribution of the a-series family of gangliosides has been observed in both pre-clinical models and human patients with neurodegenerative diseases and injuries, such as Alzheimer’s disease (AD) and strokes. Ganglioside dysregulation has been implicated as an important mechanisms driving pathology in the aging brain, yet there is little information on where and when these lipid changes occur as well as the role of dysregulation during neurodegeneration. Matrix-Assisted Laser Desorption/Ionization (MALDI) …