Nervous System Diseases Commons^™

The Rpm-1/Phr Signaling Hub Modulates Tau-Induced Neurodegeneration Through Regulation Of Microtubule Stability And Mapk Pathways In C. Elegans, Xinxing Ding

Theses and Dissertations

Neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia, are characterized by the accumulation of pathological tau proteins and progressive neuronal loss. Although research regarding tau-mediated toxicity is extensive, the specific pathology that determine whether neurons maintain homeostasis or succumb to collapse under tau-induced stress remain incompletely elucidated. A central, yet still insufficiently understood, feature of these diseases is the disruption of the microtubule (MT) cytoskeleton . The PHR protein family is evolutionarily highly conserved; within this family, RPM-1 in C. elegans functions as an intracellular signaling hub that regulates axon development, synapse formation, axon termination, and various microtubule-associated processes. This …

The Neuroprotective Effect Of Cdc42 Inhibition In The G93a Mutant Hsod1 Mouse Model Of Als, Andrea Koly

Undergraduate Theses, Capstones, and Recitals

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by the selective loss of upper and lower motor neurons, leading to muscle weakness, neuromuscular junction (NMJ) degeneration, paralysis, and eventual death due to respiratory failure. Despite extensive research, effective disease-modifying therapies remain limited, underscoring the need to identify novel molecular targets involved in ALS pathogenesis. Dysregulation of Rho family GTPases has been implicated in neurodegeneration, with Rac and Rho exerting opposing effects on neuronal survival; however, the role of the closely related GTPase Cdc42 remains poorly understood in ALS. In this study, the therapeutic potential of inhibiting …

Mapping The Neuroexposome: Integrative Analysis Of Dementia Risk Factors Through Multi-Omics And Environmental Profiling In The Egyptian Population., Mai Ahmed Saadzaghloul Othman

Theses and Dissertations

Background: Dementia represents one of the most pressing public health challenges of the twenty-first century, with the global burden projected to reach 153 million cases by 2050. Egypt, as the most populous Arab nation, faces a corresponding rise in age-related diseases, yet comprehensive data from low- and middle-income countries remain severely limited. The neuroexposome framework, integrating genetic susceptibility, environmental exposures, and metabolic alterations, offers a powerful strategy to characterize the complex interplay between internal and external risk factors for Alzheimer's disease (AD) and Alzheimer's disease Related Dementias (ADRD).

Objectives: This thesis aimed to: (1) examine the distribution of APOE alleles …

Fentanyl Mediated Distortions Of Phasic Dopamine Release Dynamics Encoding Natural Reward And Aversive Processing In The Mammalian Mesolimbic Circuit, Oliver P. Culver Iv

MUSC Theses and Dissertations

Mu opioid receptor (MOR) agonists are recognized to disinhibit tonic dopamine (DA) in the ventral striatum (VS), contributing to opioid addiction and euphoria. However, MOR agonists can also inhibit non-drug reward-seeking, and disrupt conditioned responding to aversive stimuli, a phenomenon not readily explained by tonic DA disinhibition. We hypothesized that this effect could be due in part to disruption of phasic DA responses to conditioned stimuli (CS) which critically shape and maintain behaviors during naturalistic reward and aversive processing. Because MOR effects on CS-evoked phasic DA are largely unexamined, we conducted in vivo fiber photometric recordings in water-deprived male and …

A Predictive Coding Account Of Spatial Working Memory Following Prophylactic Levetiracetam Administration Prior To Traumatic Brain Injury, Omeima Mutwali

Dissertations, Theses, and Capstone Projects

Traumatic brain injury (TBI) symptom prevention and remediation is an important area of research that would benefit vulnerable groups, including active-duty and veteran soldiers. These patients can sustain penetrative forces in fields of combat or in training, which result in focal lesions that trigger inflammatory and degenerative processes in the brain. Both primary and secondary injuries are associated with changes to cognition, behavior and affective state. This disease poses increased risk of epileptogenesis, as well. Given these outcomes, prior research has evaluated levetiracetam (LEV) as a prophylactic treatment for seizures, cognitive deficits and negative emotionality. LEV acts as a presynaptic …

Parkinson’S Disease Phenotype Stratification Using Multiple Correspondence Analysis, Kelly Astudillo

Dissertations, Theses, and Capstone Projects

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, with over 12 million people projected to be affected by 2040 (Dorsey et al., 2018). Deep phenotyping and stratification can provide useful information regarding PD pathogenesis and can aid in the  development of disease modifying therapies that aim to delay the progression or prevent the onset of neurodegeneration (Blandini et al., 2019; Smith & Schapira, 2022). Utilizing multivariate methods such as multiple correspondence analysis (MCA) permits for the simultaneous analysis of distinct data modalities. To the best of our knowledge, MCA has not been previously used to explore phenotype patterns …

Rhythms Of Hippocampal Function And Memory After Moderate Prenatal Alcohol Exposure, Lilliana May Sanchez

Psychology ETDs

Fetal Alcohol Spectrum Disorders involve morphologic and neurobiological abnormalities in offspring subjected to prenatal alcohol exposure. Although not as well studied as high exposure, moderate prenatal alcohol exposure represents the most common and undetected form in humans. While learning and memory deficits have been well characterized at the behavioral level in humans with Fetal Alcohol Spectrum Disorders and in animal models of moderate prenatal alcohol exposure, few studies have determined the circuit or systems level mechanisms of the behavioral deficits. A complete understanding of the neural bases of memory deficits after moderate prenatal alcohol exposure is needed to ultimately identify …

Quantifying Black Carbon Concentrations In Georgia And Analyzing Associated Public Health Risks, Khloe R. Osborne

Honors Theses

Quantifying Black Carbon Concentrations in Georgia and Analyzing Associated Public Health Risks

One of the most daunting challenges of the industrial world is air pollution. Within this broad spectrum, there is an inhalable particle group named PM2.5, which contains black carbon. Black carbon has evidence that supports the generation and worsening of adverse health impacts, which may include birth complications, cognitive deficits in children, pulmonary aggravation, asthma, cardiovascular issues, neurological degenerative patterns, and cancer risk. This is especially seen in vulnerable populations, like children, elderly, and those who already suffer from weakened health, many of which reside in the southern …

Targeting The Dorsolateral Prefrontal Cortex With Transcranial Direct Current Stimulation To Improve Depression And Anxiety In Parkinson's Disease, Brock Renicks

Honors Theses

The aim of this study is to observe the outcomes of transcranial direct current stimulation (tDCS) as a treatment for Parkinson’s Disease (PD). This study will primarily look at changes in depression and anxiety, as these symptoms are often comorbid with Parkinson’s Disease. Transcranial direct current stimulation is a non-invasive, very low-intensity form of electrical stimulation of the brain. It is being increasingly used as a form of treatment for Parkinson’s Disease and depression and anxiety, however the literature is ambiguous, showing mixed results throughout various studies, with no standardization of tDCS administration. To determine the effect of tDCS on …

Novel Biomarker Discovery In Multiple Sclerosis, Manisha Gangasani

Honors Theses

Multiple Sclerosis (MS) is a chronic neuroinflammatory disorder affecting the brain, spinal cord, and optic nerve. Patients experience cognitive, motor, autonomic, and emotional symptoms that often overlap with other neurological conditions, making early diagnosis challenging. Current diagnostic criteria require evidence of lesions with dissemination in time and space. Racial disparities in MS outcomes are well documented, with Black individuals often exhibiting greater disease severity, higher relapse rates, and increased disability compared to White individuals. These differences likely reflect a combination of genetic, biological, environmental, and healthcare access factors, underscoring the need to improve early diagnosis and reduce inequities in care. …

Pattern Dynamics And Stochasticity Of Brain Rhythms And Spike Trains In A Tauopathy Mouse Model Of Alzheimer’S Disease, Clarissa M. Hoffman

Dissertations and Theses (Open Access)

Systems neuroscience posits that every aspect of perceived physical reality, every aspect of animal and human behavior, and every cognitive phenomenon emerges from patterns of neuronal activity. While most researchers embrace this idea, there are major difficulties in describing and analyzing these complex neuronal dynamics—spike flows produced by cells ensembles, synchronized extracellular field oscillations, and other patterns—which limits our understanding of how the activity of individual neurons and the whole-animal cognition and behavior might be connected. In particular, we lack the approaches and even the semantics for connecting the individual cell outputs and the integrated results of their activity. Current …

Feeding The Mind: Dietary Consumption And Neural Aging, Bhavani Tuppale

Senior Theses

Neural aging is the process of physiological decline in the brain and increased vulnerability to neurodegenerative diseases. Neurodegenerative diseases such as Alzheimer’s disease are associated with aging and the interaction of genetics and lifestyle choices. Previous research studies have connected Alzheimer’s disease with dysfunction in the metabolic system. To combat age-associated dysfunctions in the metabolic system, research studies propose using the ketogenic diet, which utilizes ketone bodies as an energy source instead of glucose. The thesis analyzes literature on the effect of neural aging on various model organisms, how a ketogenic diet affects aging model organisms, and how aging and …

Contribution Of G4 Structure To Alzheimer’S Disease And Tau Pathology, Lena Michaela Kallweit

Electronic Theses and Dissertations

The occurrence of Alzheimer’s Disease (AD) is rapidly increasing as our global population ages. With the majority of therapeutic drugs in the last couple of decades failing clinical trials, new molecular targets are needed to combat the expected influx of new AD cases. AD pathogenesis is associated with abnormal protein aggregation, characterized in part by intracellular accumulation of hyperphosphorylated tau (p-tau) in neurofibrillary tangles (NFTs). RNA has been identified as a major non-proteinaceous component of NFTs and has been implicated as an active cofactor in tau aggregation and spread. Recent work has shown that aggregates from AD brains contain almost …

Examining The Association Between Ddt Exposure And Parkinson’S Disease, Hodges Mccathern

Undergraduate Honors Theses

Dichlorodiphenyltrichloroethane, commonly known as DDT, was an organochlorine pesticide widely used in the mid-20th century. It is highly stable and resistant to degradation, leading to its long-term presence in the environment. This chemical bioaccumulates in ecosystems and in human tissue, particularly adipose tissue, raising concerns about chronic exposure. Emerging research links DDT exposure to adverse neurological outcomes, including increased risk for neurodegenerative disorders such as Parkinson’s Disease. Mechanistically, DDT and its metabolites may disrupt dopaminergic neurons, induce oxidative stress, and interfere with mitochondrial function, contributing to neurotoxicity. Understanding the environmental fate of DDT and its bioaccumulative properties is essential for …

Metabolism As A Regulator Of Sleep And Cortical Activity In Health And Alzheimer’S Disease, Nicholas J. Constantino

Theses and Dissertations--Neuroscience

Metabolic flexibility is essential for maintaining normal physiological function, enabling an organism to sense, flux, utilize, and switch fuel sources in response to changing energetic availability, demand, and cellular needs. Energetic demands are state-dependent, with wake and sleep exhibiting distinct metabolic profiles. Sleep is highly sensitive to changes in metabolism and requires metabolic flexibility to both transition into and maintain sleep stability. Alzheimer’s disease (AD) is increasingly recognized as a disease of altered metabolism yet is often framed as a disease of energetic failure. We instead define AD as a disease of metabolic inflexibility, characterized not by insufficient energy availability, …

Engineering Plga Nanoparticle Size To Modulate Immune Responses After Spinal Cord Injury, Daniel J. Kolpek

University of Kentucky Doctoral Dissertations

Spinal cord injury is a severe and debilitating condition that often results in lifelong complications, including paralysis. Many of these chronic outcomes are driven by a sustained inflammatory response at the injury site, which limits tissue regeneration and functional recovery. As a result, therapeutic strategies that modulate this immune response have gained significant interest. Polymer based nanoparticle therapies have emerged as a promising approach due to their ability to interact with and influence immune cell behavior. Importantly, the physicochemical properties of nanoparticles can be precisely tuned to optimize these effects. Among these properties, size has been shown to influence key …

The Effects Of Vitamin K On Neuronal Ferroptosis, Chelsey P. Eighmey

Electronic Theses & Dissertations (2024 - present)

Dementia is a crippling illness affecting millions worldwide causing significant public health burdens with long-term care. The lack of treatment options results in many years of suffering for affected individuals and their loved ones who often become primary caretakers. Decades of study have focused on treating dementia with little-to-no success, so an emphasis is needed on attempting to prevent disease progression altogether. This research explored vitamin K as a potential strategy for prevention of dementia onset or progression through the mechanism of suppressing ferroptosis. Ferroptosis is a type of cell death suggested to contribute to the hallmark traits of Alzheimer’s …

Investigating The Role Of Traditional Chinese Herbal Medicine For Cancer Symptom Management In Older Adults: A Rapid Review, Isabelle C. Karshner

Honors Undergraduate Theses

Background: Patients with cancer often experience symptoms related to disease, complications, and treatment. One potential method of alleviating these symptoms is traditional Chinese herbal medications (TCHM). This rapid review explores the role of traditional Chinese herbal medications in treating cancer-related symptoms in older adults.

Purpose: The purpose of this rapid review is to gain and provide a better understanding of the effects of TCHM on cancer-symptom management in the older adult population. This review explores the association between TCHM and effects on cancer symptoms in older adults, including interactions, toxicity, and signs/symptoms of TCHM use that may be useful information …

What’S Sleep Got To Do With It? A Mixed Methods Exploration Of The Feasibility, Acceptability, And Initial Outcomes Of Group Cbt For Insomnia In Parkinson’S Disease, Claire M. Williams

Theses and Dissertations

Parkinson’s disease is a progressive neurodegenerative disease that is commonly associated with sleep disturbances, affecting up to 80 percent of individuals with Parkinson’s. Effective and accessible treatments for sleep problems in Parkinson’s disease remain limited. Cognitive Behavioral Therapy for Insomnia (CBTi) is a well-established, non-pharmacological treatment for insomnia but has been minimally studied in Parkinson’s populations. This study evaluated the feasibility, acceptability, and preliminary outcomes of a group-based CBTi intervention adapted for individuals with Parkinson’s disease. Participants engaged in a six-week group intervention that incorporated Parkinson’s-specific adaptations. Preliminary findings indicated that the adapted group CBTi intervention was generally feasible and …

Biofluid Biomarkers Aid In Diagnosing And Developing Improved Treatments For People With Alzheimer's Disease, Jonatan A. Lopez

University Honors Theses

Dementia is a disease in which daily life is disrupted by a loss of cognitive function. Late-onset Alzheimer's disease (AD) is the most common dementia that largely begins to affect individuals in their mid 60s or older. AD was selected as the focus of this paper because it is the most common form of dementia, accounting for 50-70% of dementia cases. A typical diagnostic approach used by physicians starts with a simple clinical test, the Mini-Mental State Examination (MMSE), when cognitive decline is suspected in a patient. Then if there is enough evidence to suggest AD, a physician would order …

Microbial Metabolite Regulation Of Microglial Ahr Signaling In Alzheimer’S Disease, Ghalya E. Alrousan

Dissertations and Theses (Open Access)

Introduction: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β plaque accumulation, neuroinflammation, and cognitive decline. Recent evidence suggests that systemic factors, particularly the gut microbiota and its metabolites, play a significant role in shaping brain immune responses, including microglial activation. However, the mechanisms linking gut dysbiosis to microglial dysfunction in AD are poorly understood. The aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor responsive to tryptophan metabolites, has recently gained attention as a key regulator of neuroinflammation and microglial function. I hypothesize that the loss of beneficial microbial AHR ligands, specifically indole derivatives, during aging and AD …

Microneedle-Based Lc-Ms/Ms Profiling Of Dermal Interstitial Fluid Reveals Early Lipid Dysregulation Contributing To Painful Neuropathy In Prediabetic And Type 2 Diabetic Rats, Srinivasa Rao Gadam

Biomedical Sciences ETDs

Painful diabetic neuropathy (PDN), a complication of type 1 and type 2 diabetes, also occurs in obesity and prediabetes, with dyslipidemia as a modifiable risk factor. The distal-to-proximal neuropathy pattern and length-dependent intraepidermal nerve fiber loss suggest peripheral contributions. We hypothesized that elevated neurotoxic lipid intermediates—diacylglycerols (DAG), free fatty acids (FFA), and acylcarnitines (CARs)—in the dermal interstitial fluid (ISF) drive metabolism-associated hyperalgesia in prediabetic and diabetic rats. Using a microneedle array (MIA) with LC-MS/MS, we profiled ISF and serum lipids from high-fat diet (HFD) and HFD + streptozotocin (STZ) rat models alongside Hargreaves testing. ISF lipid changes appeared earlier (weeks …

How Do Montessori-Based Activities Affect Behaviors For Older People With Dementia: A Literature Review, Isabel Quigley

University Honors Theses

Objectives: This literature review is meant to analyze the development on the research on Montessori-based activities for adults with dementia.

Introduction: Baby Boomers are the largest generation to enter senior age (65+) in history due to the advancement in medicine to increase life expectancy. Dementia is a neurocognitive disease that affects parts of the brain related to memory and signs typically surface around 65 years old. Dementia is not considered healthy aging. Montessori-based activities have been recently developed as an intervention to encourage a feeling of accomplishment and success for adults with dementia.

Methods: Two electronic databases …

Covid-19 And Related Adverse Neurological Complications, Hannah A. Wasson

Honors Thesis

Abstract

The COVID-19 pandemic changed the world drastically, and its impact was monumental. COVID-19 or SARS-CoV-2, or severe acute respiratory syndrome, was the virus responsible for causing such mayhem. This contagious virus can enter the body via different routes, live on surfaces for hours, and be transmitted through the air, increasing infection risk. Once it enters the body, it can trick the body into replicating the virus. From this reaction within the body, signs and symptoms follow. While the name indicates a respiratory illness, the virus can inflict injury on other parts of the body. Due to the organ systems …

Developing Adaptive Clothing For Patients With Advanced Als Disease, Kadence D. Trosper

Apparel Merchandising and Product Development Undergraduate Honors Theses

In 2017, over 30,000 people were battling with Amyotrophic Lateral Sclerosis, also known as ALS. ALS is a progressive neurodegenerative disease that affects nerve cells within the brain, brain stem, and spinal cord (ALS Association, 2023). The individual’s brain loses connection with muscles, slowly taking away one’s ability to walk, talk, eat, and eventually breathe. The currently is no cure for this disease or even treatment to halt the progression, however the treatment available can help ease the symptoms. Despite the physical challenges associated with ALS, there is a significant lack of adaptive clothing options that provide comfort, functionality, and …

Rod Photoreceptor Regeneration In A Zebrafish Model With Retinitis Pigmentosa, Eyad Shihabeddin

Dissertations and Theses (Open Access)

A cellular hallmark of inherited retinal degenerative diseases is progressive loss of photoreceptors until one is completely blind. Unlike mammalian models, Zebrafish have the ability to naturally regenerate their neurons after injury or disease is detected. We have generated a zebrafish model with the most common autosomal dominant form of the inherited retinal degenerative disease known as Retinitis Pigmentosa. We utilize immunohistochemistry, single-cell RNA sequencing, several analysis tools, behavioral assays and oligonucleotides to characterize our zebrafish model and identify the transcription factors necessary for rod photoreceptor regeneration. We show that our zebrafish model has continuous degeneration and regeneration of rod …

Exploring The Immunologic Consequences Of Atrx Deficiency In Glioma, Benjamin Whitfield

Dissertations and Theses (Open Access)

ATRX is a key chromatin regulator that is frequently mutated across multiple cancer types. One of the most common ATRX-mutated tumor types is the adult-type glioma, IDH-mutant, Astrocytoma. It is known that ATRX mutation leads to increases in DNA damage, replication stress, and global epigenetic regulation at a cell level; however, less is known about the impact of ATRX mutation on immune signaling. Furthermore, little is known about the interaction of ATRX loss with gain-of-function mutations in IDH. In this paper we set out to explore the impact of ATRX loss on immune signaling in gliomas, both in the context …

Remission Of Multiple Sclerosis Symptoms In Pregnancy: A Neurological Mystery Of Chronic Disease, Brandon Olsen

Honors Capstones

Multiple Sclerosis is defined as an autoimmune disorder of the central nervous system being attacked by the immune system leading to the destruction of the protective myelin cells around nerves according to Cleveland Clinic. Pregnancy wages a high level of stress on the female body with changes in regulation of many body systems, stress is one of the major precursors to having a “flare-up” of symptoms of MS, and women are three times more likely than men to experience multiple sclerosis. Assumptions would suggest that pregnancy with MS would cause constant experience of symptoms including pain and loss of ability …

Developing And Validating Brain Tumor Organoid Models To Evaluate Novel Therapeutics In Vitro, Dev P. Patel

Senior Theses

Glioblastoma (GBM), a World Health Organization Grade IV brain tumor, remains one of the most aggressive and treatment-resistant malignancies. It is characterized by rapid proliferation, deep infiltration, and a high level of genotypic and phenotypic heterogeneity. Despite advancements in medical technology and neuro-oncology, GBM remains one of the most treatment-resistant cancers with a median survival rate of only nine months post-diagnosis and less than 5% of patients surviving beyond 5 years of diagnosis. The standard treatment constitutes maximum surgical resection followed by chemotherapy and radiation. These therapeutic strategies are blocked by significant challenges like the blood-brain barrier (BBB), and intratumoral …

The Impact Of Diabetes On Neurovascular Integrity: A Special Focus On Pericytes And Endothelin-1, Mia Edgerton

MUSC Theses and Dissertations

Diabetes increases the risk of stroke and Vascular Contributions to Cognitive Impairment and Dementia (VCID). Diabetes also dysregulates the endothelin (ET) system. ET-1-mediated constriction of brain microvascular pericytes (BMVPCs) has been shown to contribute to brain hypoperfusion. However, there is a loss of BMVPCs in VCID, but underlying mechanisms of pericyte degeneration are poorly studied. ETA receptor activation can instigate phenotypical changes and cellular senescence in endothelial cells. . There is also emerging evidence that ETB receptor agonism improves outcomes in patients with cerebral ischemic stroke, but long-term effects, especially in diabetes, are unknown. Therefore, this study aimed to determine …