Neurosciences Commons^™

Evaluation Of Aging And Genetic Mutation Variants On Tauopathy, Amber M. Tetlow

USF Tampa Graduate Theses and Dissertations

Alzheimer’s disease (AD) is characterized by amyloid β plaques and neurofibrillary tau tangles (NFTs). While research has demonstrated amyloid pathology occurs prior to tau pathology, or tauopathy, tau has proven to be more toxic. Tauopathy is associated with cognitive declines and neurodegeneration. These findings have highlighted the importance of further understanding tauopathy. In the progression of tauopathy, there is an observable immune response that can be measured by glial cells such as microglia. Activated microglia are known to exacerbate tauopathy rather than reducing the pathology. Research has indicated that with increased age there is an increased risk for AD-related tauopathy …

Immune Modulation As A Therapeutic Target In An Α-Synuclein Model Of Parkinson’S Disease, Meena Subhashini Subbarayan

USF Tampa Graduate Theses and Dissertations

Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting about 1.5 million people in the United States with more than 60,000 people diagnosed each year. It is classically characterized by four major symptoms: tremor, postural instability, stiffness in joints, and slow movement (bradykinesia). Pathologically PD is characterized by up to 70% loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) of midbrain and accumulation of presynaptic protein called α-synuclein (α-syn) within dopaminergic neurons that extend to the striatum. This disrupts the nigrostriatal pathway leading to the motor symptoms seen in PD patients. Microglia, the innate immune cells …

Ssh1 Impedes P62/Sqstm1 Flux And Tau Clearance Independent Of Cofilin Activation, Cenxiao Fang

USF Tampa Graduate Theses and Dissertations

Accumulation of toxic protein assemblies and damaged mitochondria are key features of neurodegenerative diseases, which arise in large part from clearance defects in the autophagy-lysosome system. The autophagy cargo receptor p62/SQSTM1 plays a major role in the clearance of ubiquitinated cargo through Ser403 phosphorylation by multiple kinases. However, no phosphatase is known to physiologically dephosphorylate p62 on this activating residue. RNAi-mediated knockdown and overexpression experiments using genetically encoded fluorescent reporters and defined mutant constructs in cell lines, primary neurons, and brains show that SSH1, the canonical cofilin phosphatase, mediates the dephosphorylation of phospho-Ser403-p62, thereby impairing p62 flux and phospho-tau clearance. …

Indicators Of Mild Cognitive Impairment Associated With Language Processing And Production, Diana Julbe-Delgado

USF Tampa Graduate Theses and Dissertations

The research purpose of the present study was to (1) examine cognitive-linguistic features related to processing and production across a series of tasks that are representative of everyday discourse and (2) compare older adults with and without mild cognitive impairment (MCI) across linguistic features. Twenty-seven participants, including 12 individuals with- and 15 individuals without MCI, were enrolled from a larger study (Hudak et al., 2019). Cognitive status was initially assessed as part of the larger study using the Montreal Cognitive Assessment (MoCA; Nasreddine et al., 2005). Participants who scored ≤ 25 on the MoCA received a standardized neuropsychological evaluation and …

Hybrid Electro-Plasmonic Stimulation Of Primary Neurons, Ratka Damnjanovic

USF Tampa Graduate Theses and Dissertations

Biomedical prosthetics utilizing electrical stimulation have limited, effective spatial resolution due to spread of electrical currents to surrounding tissue, causing nonselective stimulation. So, precise spatial resolution is not possible for traditional neural prosthetic devices, such as cochlear implants. More recently, alternative methods utilize optical stimulation, mainly infrared, sometimes paired with nanotechnology for stimulating action potentials, which has its own drawbacks, as it may heat surrounding tissue. Recently, we employed plasmonic stimulation methods utilizing gold nanoparticle-coated nanoelectrodes to convert visible light pulses into localized surface plasmon resonance transduction for stimulation of electrically excitable cells, which had limited success. Here, we report …

Mass Spectrometry Discovery-Based Proteomics To Examine Anti-Aging Effects Of The Nutraceutical Nt-020 In Rat Serum, Samantha M. Portis

USF Tampa Graduate Theses and Dissertations

Aging is a complex physiological process that leads to the deterioration of all cells and tissues throughout the body. Aging is a major risk factor for the onset of many degenerative diseases in both the central nervous system (CNS) and the periphery, but even nonpathological aging (“normal” aging) is associated with chronic inflammation, oxidative stress, and decreased stem cell proliferation and regenerative capacity. This decreased regenerative capacity in stem cell niches is thought to be a key component underlying the aging process and many disease states associated with aging.

While the exact biological mechanisms underlying impaired stem cell proliferation and …

An Eye Opener In Stroke: Mitochondrial Dysfunction And Stem Cell Repair In Stroke-Induced Retinal Ischemia, Hung Vu Thien Nguyen

USF Tampa Graduate Theses and Dissertations

Stoke is a leading cause of disability and mortality across the globe, making it a global health crisis. However, treatments for stroke remain limited with narrow therapeutic time window. Visual impairment negatively affects patients’ quality of life. During stroke, the disruption in blood flow might affect both brain and eye resulting in cerebral and retinal ischemia. Currently, there is a lack of treatment option that targets both cerebral and retinal ischemia. Ischemic stroke pathology is complex and multiphasic. The ischemic event is followed by a secondary cascade of inflammatory cytokines exacerbating the initial focal injury and expanding into the penumbra. …

Mapping Reward Values To Cues, Locations, And Objects: The Influence Of Reward Associations On Visual Attention, Constanza De Dios

USF Tampa Graduate Theses and Dissertations

Previous work has attempted to fit reward-driven attentional selection as being exogenous (stimulus-driven) or endogenous (goal-driven). However, recent work suggests that reward’s effects on attention depend on the type of stimulus feature that the motivational information is imparted during learning (incentive salience). If true, then reward should not be limited to solely impacting early perceptual or late categorization processes attention. The current study used event-related potentials (ERPs) to test the idea that reward’s effects on attention depend on the process that the reward information is embedded – early perceptual or late categorization. Results demonstrated reward-driven effects on perceptual representation when …

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 …

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 …

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 …

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 …

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 …

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 …

Astaxanthin Attenuates Mptp Induced Neurotoxicity And Modulates Cognitive Function In Aged Mice, Beth Grimmig

USF Tampa Graduate Theses and Dissertations

Parkinson’s disease is the second common neurodegenerative disease and is most frequently diagnosed in individuals over 60. There are no available medications that can prevent or restore the loss of neurons that correspond to motor impairments in patients. Identifying novel therapeutic compounds that are capable of slowing and reversing the extensive neurodegeneration that occurs in PD remains an important goal of the field. While basic research has identified potential therapeutic agents, studies often use young model organisms to demonstrate efficacy of the target compound. This approach ignores the impact of the aged CNS on the disease process, and likely contributes …

Contributions Of Appetitive And Aversive Motivational Systems To Decision-Making, Heather E. Soder

USF Tampa Graduate Theses and Dissertations

Optimal decision-making entails outcome evaluation, comparing received costs and benefits with predicted costs and benefits. The anterior cingulate cortex (ACC), a brain area with major connections to the appetitive and aversive motivation systems, may provide the neural substrate of this evaluation process. One way to measure the relative contribution of these systems on decision-making is to measure individual differences in risk-taking behaviors. For individuals who make risky choices, this evaluation step may be biased: some show a preference for immediate, short-term rewards (increased appetitive system), while devaluing the long-term consequences of their choices (decreased aversive system). However, most studies supporting …

A Longitudinal Study Of The Effects Of Cognitive Awareness Training On Transaction Processing Accuracy: An Introduction To The Ace Theoretical Construct, John Townsend

USF Tampa Graduate Theses and Dissertations

This study examines the impact of Cognitive Awareness training on transaction processing accuracy rates within the US Financial Services Industry. Grounded in the theories of Inattentional Blindness and Error Management Culture, this paper supports and extends both theories through the development of a new theoretical construct. The ACE Construct is a novel approach that combines cognitive science, organizational development, and operational efficiency practices into a single approach designed to improve transaction processing accuracy. The study involved the design and implementation of a novel training program, with performance data observations sampled over seven months, to evaluate the impact of Cognitive Awareness …

Force Compensation And Recreation Accuracy In Humans, Benjamin Rigsby

USF Tampa Graduate Theses and Dissertations

As industry becomes increasingly reliant on robotic assistance and human-computer interfaces, the demand to understand the human sensorimotor system’s characteristics intensifies. Although this field of research has been going on for over a century, new technologies push the limits of the human motor system and our knowledge of it. With new technologies come new abilities, and, in the area of medical care and rehabilitation, the need to expand our knowledge of the sensorimotor system comes from both the patient and physician.

Two studies relating to human force interaction are presented in this thesis. The first study

focuses on humans’ ability …

An Anatomical Study Of The Hyperpallium Densocellulare In The Pigeon (Columba Livia), Sara Leilani Kellogg

USF Tampa Graduate Theses and Dissertations

The hyperpallium densocellulare (HD) is an avian cerebral structure, the origin of which remains unclear and considered to be critical to the understanding of the non-mammalian forebrain evolution. The main goal of this investigation was to clarify the anatomical characteristics and behavioral implications of HD, which had been assumed to be a homogeneous unitary entity. This project had three specific aims: 1) To identify possible subdivisions of HD in terms of cytoarchitecture, Substance P distribution, and connections based on unpublished (Aim 1a) as well as published data (Aim 1b); 2) To identify the unknown connections of these subdivisions by using …

Multi-Scale Spatial Cognition Models And Bio-Inspired Robot Navigation, Martin I. Llofriu Alonso

USF Tampa Graduate Theses and Dissertations

The rodent navigation system has been the focus of study for over a century. Discoveries made lately have provided insight on the inner workings of this system. Since then, computational approaches have been used to test hypothesis, as well as to improve robotics navigation and learning by taking inspiration on the rodent navigation system.

This dissertation focuses on the study of the multi-scale representation of the rat’s current location found in the rat hippocampus. It first introduces a model that uses these different scales in the Morris maze task to show their advantages. The generalization power of larger scales of …

Receptor-Associated Protein (Rap) Models In Vivo Reelin Haploinsufficiency: Implications In Schizophrenia, Jamileh Ahmed

USF Tampa Graduate Theses and Dissertations

The “two-hit” schizophrenia hypothesis suggests genetic and environmental abnormalities interrupt early CNS function. This increases vulnerability of a “second hit” and schizophrenia onset. Chronic stress and decreased Reelin signaling are reportedly associated with schizophrenia. Heterozygous Reeler Mice (HRM) show a 50% reduction in Reelin and display major schizophrenia phenotypes. Receptor-Associated Protein (RAP) blocks ligand-association to Reelin receptor Apolipoprotein E receptor 2 (ApoER2). In this study, we sought to replicate major heterozygous reeler mouse (HRM) phenotypes using in vivo RAP studies to establish an experimental in vitro model. Using an in vitro model, we investigated the effects of chronic stress and …

Acetaminophen Associated Neurotoxicity And Its Relevance To Neurodevelopmental Disorders, Seol-Hee Kim

USF Tampa Graduate Theses and Dissertations

Autism is a lifelong neurodevelopmental disorder. The etiology of autism still remains unclear due to the heterogeneous and complex nature of the disorder, however synergistic actions between genetic components and environmental factors have been suggested. Acetaminophen (APAP) is one of the most popular over-the-counter drugs that possess antipyretic and analgesic effects. It is considered a relatively safe and effective within therapeutic doses. Recently, early exposure to APAP has been suggested to be one of the underlying cause of autism. Children are often prescribed APAP to lessen fever or irritability after vaccination during the first year, and APAP may adversely affect …

Neuropeptide Modulation Of The Large Conductance Potassium (Bk) Channel In The Auditory System: Therapeutic Implications For Age-Related Hearing Loss, Ellliott James Brecht

USF Tampa Graduate Theses and Dissertations

The auditory temporal processing deficits associated with age-dependent hearing decline have been increasingly attributed to issues beyond peripheral hearing loss. Age-related hearing loss (ARHL), also known as presbycusis, is linked with changes in the expression of both excitatory and inhibitory neurotransmitters in the central auditory system. There are also age-related changes in the expression and function of the ion channels which mediate action potential firing. The slow, Ca²⁺ activated, K⁺ channels of the BK-type are essential in controlling both neurotransmitter release and neural communication via alteration of action potential durations, firing frequency, and neural adaptation. There are many …

The Potential Role Of Antiretroviral Efavirenz In Hiv Associated Neurocognitive Disorders, Lecia Ashanna Moya Brown

USF Tampa Graduate Theses and Dissertations

The prevalence of milder forms of HIV-associated neurocognitive disorders (HAND) is rising despite combination antiretroviral therapy (cART). Efavirenz (EFV) is among the most commonly used antiretroviral drugs globally, but causes neurological symptoms that may interfere with adherence and reduce tolerability, and may have central nervous system (CNS) effects that contribute in part to HAND in patients on cART. Thus we evaluated a commonly used EFV containing regimen: EFV/zidovudine (AZT)/lamivudine (3TC) in murine N2a cells transfected with the human “Swedish” mutant form of amyloid precursor protein (SweAPP N2a cells) to assess for promotion of amyloid-beta (Aβ) production (Chapter 3). Treatment with …

Tau-Directed Immunotherapy For Alzheimer’S Disease, Sulana Kay Schroeder

USF Tampa Graduate Theses and Dissertations

Alzheimer’s disease (AD) is the leading cause of dementia, accounting for 50 to 80 percent of dementia cases, and the prevalence of the disease is projected to increase significantly with time. AD is characterized by severe cognitive decline with age, ultimately requiring continued caregiving and eventually death. The pathology of AD is characterized by the presence of extracellular amyloid plaques, intracellular neurofibrillary tangles (NFT) composed of hyperphosphorylated tau protein, neuron loss, and evidence of inflammation indicated by the presence of reactive microglia and astrocytes. Frontotemporal Lobe Dementia (FTLD) is a rare form of dementia that is related to AD, most …

Mass-Spectrometry Based Proteomics Of Age-Related Changes In Murine Microglia, Antwoine Flowers

USF Tampa Graduate Theses and Dissertations

The last century has seen a steady increase in the extension of the average lifespan. This has concomitantly produced higher incidences of age-related chronic degenerative diseases like Alzheimer’s and Parkinson’s diseases. Age is the single greatest risk factor for the development of not just these degenerative conditions but cancer as well. The aged niche undergoes a number of maladaptive changes that allow underlying conditions to present and progress. Exactly which changes, contribute to the progression of which disease is currently an area of intense study. However, these answers often present therapeutic targets for disease prevention. Age is characterized by a …

The Effects Of Synthetic And Dietary Therapeutics On Learning, Memory, Motor Coordination, And Seizure In An Angelman Syndrome Mouse Model, Stephanie Lynn Ciarlone

USF Tampa Graduate Theses and Dissertations

Angelman syndrome (AS) is a rare genetic and neurological disorder presenting with severe developmental delay, ataxia, epilepsy, and lack of speech. AS is associated with a neuron-specific loss of function of the maternal UBE3A allele, a gene encoding an E3 ubiquitin ligase. Currently, no cure exists for this disorder; however, recent research using an AS mouse model suggests that pharmacological intervention is plausible, and can alleviate some of the detrimental phenotypes reported in AS patients.

Although there is no curative treatment for AS, seizure medication and behavioral therapies are most commonly prescribed in order to minimize symptoms. However, these options …