Hdac5 Enzymatic Activity Regulates Scn4b Expression To Control Relapse-Like Cocaine Seeking, Daniel J. Wood

MUSC Theses and Dissertations

Substance Use Disorder (SUD) is a relapsing disorder characterized by repeated seeking and use of psychoactive substances despite negative consequences to the individual. Epigenetic changes within the medium spiny neurons (MSNs) of the nucleus accumbens (NAc) are thought to underly the lasting propensity to relapse in SUD. The epigenetic enzyme histone deacetylase 5 (HDAC5) in NAc MSNs limits the formation of reward-cue associations in rodent models of drug seeking, but not sucrose seeking, leading to decreased relapse-like behavior. However, whether HDAC5 reduces drug seeking behavior through its own deacetylase activity or through the recruitment of co-repressors is unknown. Furthermore, these …

Optimizing Interventions For Major Depressive Disorder And Provider Burnout: Self-Speak Exercise Dosing (Sed), Laureen Maloney-Gepfert

Lynchburg Journal of Medical Science

ABSTRACT

Major Depressive Disorder (MDD) is ranked highest among mental illnesses in the United States (US) and significantly contributes to the mental health care crisis. Patients experience resistance to pharmacologic interventions, side effects, co-morbidities, and mental health provider shortages. Subsequently, 33 % of Serious Mental Illnesses (SMIs) are being redirected to Primary Care Providers (PCPs). Concurrently, prescriber mental health is in crisis. Growing workloads for physicians and Advanced Practice Providers (APPs) have increased provider burnout syndrome (BOS). Major Depressive Disorder and BOS are positively affected by exercise, Cognitive Restructuring (CR), and Behavioral Activation (BA). Sports medicine and psychology research shows …

Effects Of Social Isolation On Locus Coeruleus Opioid Receptor Expression And Affective Behavior, John Tkaczynski, Jordan Riser, Maya Patel, Nicole Shellenbarger, Jin Park, Daniel Manvich, Daniel J Chandler

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Social isolation is a stressor that impairs homeostatic neuroendocrine functions and is associated with the development of several mood disorders characterized by persistent negative affect. Persistent feelings of loneliness have been growing public health concerns for several years and were greatly exacerbated by the onset of the COVID-19 pandemic. The problem has grown so severe the U.S. Surgeon General recently declared loneliness to be an epidemic health concern that is associated with poor mental and somatic health outcomes. Therefore, identifying mechanisms of neuroadaptation that contribute to the development of persistent negative affect is a critical step in the identifying better …

Neuromodulation Techniques For Drug-Resistant Epilepsy: Effects On Seizures And Quality Of Life, Kevin Garcia Valdez, Anesu Karen Murambadoro, Megan W. Szobody, Blake C. Martin, Kory D. Punch, Tori Sayers, Tirath Patel, Nina Mourao, Sriya Gullapalli, Nikhilesh Anand, Bharathi S. Gadad

Research Symposium

Introduction: Although there are over twenty antiseizure drugs currently available, around one third of patients with epilepsy do not benefit from these medications. Patients with drug-resistant epilepsy (DRE) experience higher rates of hospitalization, notable decline in cognitive and physical abilities, diminished quality of life, and sudden unexpected death. Neuromodulation techniques such as Vagus Nerve Stimulation (VNS), Responsive Neurostimulation (RNS), and Deep Brain Stimulation (DBS) are quickly emerging as alternative and adjunct therapies for epilepsy, offering patients and physicians a new avenue of treatment. Despite their promise, a notable gap exists in comprehensive, comparative data assessing the efficacy and suitability of …

Microglial Disruption In Young Mice With Early Chronic Exposure To Lead, Christina Sobin, Mayra Flores Montoya, Natali Parisi, Tanner Schaub, Miguel Cervantes, Rodrigo Armijos

Departmental Papers (PH)

The mechanisms by which early chronic lead (Pb) exposure alters brain development have not been identified. We examined neuroimmune system effects in C57BL/6J mice with Pb exposure, including levels that may be common among children in lower socioeconomic income environments. Pups were exposed via dams’ drinking water from birth to post-natal day 28 to low, high or no Pb conditions. We compared gene expression of neuroinflammatory markers (study 1); and microglial mean cell body volume and mean cell body number in dentate gyrus, and dentate gyrus volume (study 2). Blood Pb levels in exposed animals at sacrifice (post-natal day 28) …

In-Silico Modeling And Characterization Of Kcc2 Protein Interaction With A Small Molecule Direct Agonist Identifies Potential Binding Sites For Modulating Behaviors Associated With Substances Of Abuse, William Hai Dang Ho, Alfred Amendolara, Kenyon Mitchell, Jaden Miner, Ruth Northcott, Braxton Bingham, Andrew J. Payne

Annual Research Symposium

Purpose

KCC2 is a potassium-chloride cotransporter that plays a critical role in neuronal function by regulating GABAergic signaling via chloride gradients. Maintaining this concentration gradient is crucial for balancing excitation and inhibition in the brain. While KCC2 dysregulation has been implicated in epilepsy and seizures, recent studies suggest that KCC2 inhibition results in phenotypes mirroring those seen in chronic opioid dependence. As such, increasing evidence support KCC2 being a potential therapeutic target for modulating behaviors associated with substances of abuse. Currently, only a few direct small molecule agonists against KCC2 have been reported, and no definitive active site on the …

Investigating The Effects Of Resveratrol On Opioid-Induced Hyperalgesia, Bryana Cox, Thien Do, Ashlyn Hughes, Zane Kingsbury, Keara Leroy, Andrew J. Payne

Annual Research Symposium

Opioid-induced hyperalgesia (OIH) is an adverse effect of chronic opioid therapy, characterized by increased sensitivity to pain. This study will seek to determine if using resveratrol supplementation as an indirect enhancer to increase the expression of the KCC2 membrane transporter can alleviate the symptoms of OIH in human subjects.

Two-Year Follow-Up Of Gait And Postural Control Following Initiation Of Recombinant Human Tripeptidyl Intracerebroventricular Enzyme Replacement Therapy In Two Atypical Cln2 Patients, Rahul Soangra, Marybeth Grant-Beuttler, Harriet Chang, Raymond Y. Wang

Physical Therapy Faculty Articles and Research

Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rapidly progressive neurodegenerative disorder leading to premature mortality. Ambulatory CLN2 patients typically receive standard of care treatment through biweekly intracerebroventricular (ICV) enzyme replacement therapy (ERT) involving recombinant human tripeptidyl peptidase 1, known as cerliponase alfa (Brineura^®, Biomarin Pharmaceuticals). This study longitudinally assessed the impact of ICV cerliponase alfa ERT on gait, and postural control across a two-year span in two siblings diagnosed with atypical CLN2 disease. Both participants, ID01 (18 years and 8 months old at enrollment) and ID02 (13 years and 3 months old at enrollment), exhibited symptomatic characteristics …

Impact Of Tranexamic Acid On Patient Outcomes In Intracranial Hemorrhage: A Review, William G. Johnson

The PA Department Journal of Medical Science

Introduction: Intracranial hemorrhage is a medical emergency that remains a significant source of death and disability for patients globally. Tranexamic acid has shown promise in treating trauma related bleeding loss in various settings. This study aims to evaluate its role in the management of intracranial hemorrhages.

Methods: A review of data in the PubMed National Library of Medicine was conducted to find relevant and reputable studies related to this topic. Using the search “tranexamic acid AND intracranial hemorrhage*” and the following filters: last 5 years, free full text, English language, including RCTs, meta-analyses, and systematic reviews, 13 results …

Deep Dive In Sound Filtering, Cecilia Zoutewelle

A. The Science of Sound

A 7-page report, with illustrations and bullet-point summaries, on the ways we filter sounds as part of the standard process of hearing. Includes brief considerations of evolution, selective listening in conversations, and listening bias.

Optimizing Decision-Making In A Cerebral Palsy Model Using Reinforcement Learning, Richard Ampah

Pitzer Senior Theses

This study presents an original interdisciplinary investigation into how reinforcement learning (RL) can model motor and cognitive defects and potentially improve motor and cognitive functions in individuals with cerebral palsy (CP), a non-progressive neurological disorder that impairs movement and adaptability. Integrating computational neuroscience and machine learning, the research applies policy gradient methods and Markov Decision Processes (MDPs) to simulate adaptive learning in agents with and without CP-related constraints.

The central aim is to compare the cumulative rewards of optimal policies, derived from value iteration, and human-like learning policies using the REINFORCE algorithm, both with and without the Bellman baseline. The …

Immune Dynamics And B Cell Contributions To Neuroplasticity And Recovery After Stroke, Thomas A. Ujas

Theses and Dissertations--Neuroscience

This dissertation explores the dynamic interplay between the immune system and the brain across stroke and aging using clinical, post-mortem, and pre-clinical models. The immune system plays critical roles in shaping brain function, responding to injury, and mediating recovery. These studies aim to enhance our understanding of neuroimmune dynamics across spatial and temporal dimensions.

In the first part, we conducted longitudinal sampling of aneurysmal subarachnoid hemorrhage (aSAH) patients to track immune cell and cytokine changes at days 3, 5, 7, 10, and 14 post-stroke, with a focus on delayed cerebral ischemia (DCI), a common complication. We observed distinct temporal patterns, …

Comparative Efficacy Of Hallucinogens In Treating Mood Disorders Through A Meta-Analysis Of Symptom Reduction, Dosage, And Duration, John Marco D.F. Muniz

Honors Undergraduate Theses

Background: Hallucinogens including psilocybin, lysergic acid diethylamide (LSD), ketamine, N,N-dimethyltryptamine (DMT) (as ayahuasca), have re-emerged as potential rapid-acting treatments for mood disorders. We conducted a meta-analysis of placebo-controlled trials evaluating their efficacy in depression and anxiety disorders. Methods: A systematic review identified 12 trials (Total ≈ 670) meeting inclusion criteria (randomized, placebo-controlled). Data on Cohen’s d and Hedges’ g effect sizes for depression- and anxiety-related outcomes were extracted. We computed pooled effect sizes (weighted by sample size and inverse variance), performed subgroup analyses by drug, diagnosis, follow-up duration, and outcome measure type, and assessed heterogeneity (I², Q …

Alteration Of Peripheral Cytokines In Alzheimer’S Disease, Zhengshi Yang

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with the clinical symptoms of gradual cognitive decline and memory loss. Biologically, abnormal accumulation of Aβ (Aβ) plaque and tau tangles in the brain are the core pathological hallmarks in AD. Although inflammatory response is not specific to AD, emerging evidence suggests that the disrupted innate immune system within the central nervous system, particularly microglial activation, might act as the bridge linking Aβ aggregation to pathological phosphorylation and aggregation of tau. The inflammatory response was suggested to initially have a neuroprotective role of attempting to clear Aβ plaques, and then become neurotoxic …

Delineating Genetic Influences On Neurodegenerative Disorders And Infectious Diseases Through Advanced Computational Methods, Xiaowei Zhuang

UNLV Theses, Dissertations, Professional Papers, and Capstones

Genetics plays a critical role in understanding the molecular mechanisms underlying neurodegenerative disorders and pathogen evolution in infectious diseases. For example, identifying genetic variants associated with a disease phenotype uncovers functional pathways that could lead to potential drug targets and therapeutic interventions. In addition, tracking the genetic evolution of pathogens enables early detection and warning of infectious disease outbreaks. In both applications, given the large amount of genetic data, advanced computational methods, including longitudinal and multivariate models, could significantly boost the statistical power and capture interrelationships among traits, environmental factors and genetic influences. This dissertation focuses on four applications of …

Observing The Impacts Of Different Diets On Clinical Outcomes In Patients With Alzheimer's Disease: A Scoping Review, Erjola Toska, Alessandra Ottley, Quinn Jackson, Rachel Fricker, Alexa Carleo, Gabriella Cutrali, Olivia D’Alessio, Raquel Rossman, Samuel Kruchakov, Abraham Edelstein, Lubov Nathanson

HCA-NSU MD Research Day

Observing the Impacts of Different Diets on Clinical Outcomes in patients with Alzheimer's disease: A Scoping Review Authors: Quinn Jackson, OMS-III; Rachel Fricker,OMS-III; Erjola Toska, OMS-III; Alessandra Ottley,OMS-III; Alexa Carleo,OMS-III; Gabriella Cutrali, OMS-III; Olivia D’Alessio, OMS-III; Raquel Rossman, OMS-III; Samuel Kruchakov, OMS-III; Abraham Edelstein,OMS-III; Lubov Nathanson, Ph.D. Program: Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Florida Objectives: This study aimed to assess the literature published from 2013 to 2023 on the impact of diet on Alzheimer’s Disease (AD). Background: AD is primarily marked by β-amyloid plaques and neurofibrillary tangles, which impair neuronal synapses, leading to memory …

Use Of Electrical Bone Growth Stimulators In High-Risk Patients Following Spinal Fusion, Soumya Malhotra, Khavir Sharieff

HCA-NSU MD Research Day

Title: Use of Electrical Bone Growth Stimulators in High-Risk Patients Following Spinal Fusion Authors: Soumya Malhotra, BA., MS1 & Khavir Sharieff, DO, MBA2 1Class of 2027, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Fort Lauderdale, FL 2Assistant Professor of Surgery, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Tampa Bay, FLNova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine Objective: This study aimed to elucidate the advantages of EBGSs following high-risk spinal fusions. Background: Pseudarthrosis is a condition where bones fail to fuse after an injury or surgery. It causes significant …

The Role Of The Basolateral Nuclear Complex & Central Nucleus Of The Amygdala In Fear-Conditioned Responses To External Stimuli And Anxiety Responses, Oluwaseyi A. Adelakun

Senior Theses

This thesis reviews the role of the amygdala, particularly the basolateral nuclear complex (BLA) and central nucleus (CeA), in fear-conditioned responses and generalized anxiety disorder (GAD). By investigating the neurological and physiological mechanisms that influence the amygdala’s fear and anxiety responses, further connections can be made between this region and other notable brain regions, like the prefrontal cortex (PFC). We review both human and rodent models to explore the overlap between the two and explore various therapeutic interventions that regulate amygdalar activity and therefore mitigate anxiety symptoms. Key research into the patient SM, who lacks fear responses due to bilateral …

Cortisol And Alpha-Synuclein Stability In Saliva Under Varying Storage And Handling Conditions, Mo Zheng, Sujata Srikanth, Jeremiah Carpenter, Delphine Dean

Journal of the South Carolina Academy of Science

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor impairments and non-motor symptoms, significantly impacting patients' quality of life. Currently, cerebrospinal fluid (CSF) is the primary biofluid used for PD biomarker studies, notably α-synuclein, despite the invasive nature of lumbar puncture procedures. Recent work has shown that some of these PD biomarkers have been measured in saliva. As an alternative to CSF, saliva can be non-invasively self-collected by patients repeatedly over time to monitor biomarker levels. However, the stability of these biomarkers in saliva needs to be evaluated before saliva can be considered for patient self-collection studies. Therefore, …

Multimodal Mixing Convolutional Neural Network And Transformer For Alzheimer’S Disease Recognition, Junde Chen, Yun Wang, Adnan Zeb, M. D. Suzauddola, Yuxin Wen

Engineering Faculty Articles and Research

Early recognition of Alzheimer’s disease (AD) and its precursor state, mild cognitive impairment (MCI), is pivotal in interrupting the progression of the disease and providing suitable treatment. Recent development in deep learning techniques has drawn great research attention for improving the efficacy of AD recognition. However, numerous current methods solely utilize data from a single auxiliary domain, limiting their ability to harness valuable intrinsic insights from multiple domains. To cope with the challenge, this paper is devoted to establishing an innovative multimodal medical data fusion model, termed as MMDF, to perform Alzheimer’s disease recognition. Multimodal data including clinical records and …

Epidural Stimulation For Urogenital Dysfunction In The Spinal Cord Injured Rat., Natasha Lorraine Wilkins

Electronic Theses and Dissertations

Spinal cord injury (SCI) is a devastating, life changing event that greatly impacts quality of life. SCI can have body-wide, multi-system consequences including dysfunction within the urogenital system. Challenges with the urinary system include urinary incontinence, urine retention, and detrusor-sphincter dyssynergia all of which require maintenance through the regular use of catheters. Sexual dysfunction in men, who comprise nearly 80% of the SCI population, includes erectile dysfunction, anejaculation, retrograde ejaculation, poor expulsive force during ejaculation, and poor sperm quality. The treatment for sexual function in SCI men is focused more on fertility through the collection of sperm for insemination procedures …

The Effects Of Non-Invasive Brain Stimulation On Excitability Of The Primary Motor Cortices And Complex Motor Task Learning, Erik Woodruff Wilkins

UNLV Theses, Dissertations, Professional Papers, and Capstones

Transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) are promising non-invasive brain stimulation techniques, particularly for clinical applications involving altered or impaired motor function, such as in stroke and Parkinson’s disease. Although tDCS and tACS are different modalities, both forms of stimulation operate on the same principle - weak electrical currents are delivered through electrodes placed on the scalp in specific configurations known as “montages”. The most commonly used montage for targeting the primary motor cortex (M1) is the M1-SO configuration. This montage leverages the established observation that cortical regions directly beneath the anode generally increase in …

In Search Of The Locus Coeruleus: Guidelines For Identifying Anatomical Boundaries And Electrophysiological Properties Of The Blue Spot In Mice, Fish, Finches, And Beyond, Amelien Vreven, Gary Aston-Jones, Anthony E Pickering, Gina R Poe, Barry Waterhouse, Nelson K Totah

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Our understanding of human brain function can be greatly aided by studying analogous brain structures in other organisms. One brain structure with neurochemical and anatomical homology throughout vertebrate species is the locus coeruleus (LC), a small collection of norepinephrine (NE)-containing neurons in the brainstem that project throughout the central nervous system. The LC is involved in nearly every aspect of brain function, including arousal and learning, which has been extensively examined in rats and nonhuman primates using single-unit recordings. Recent work has expanded into putative LC single-unit electrophysiological recordings in a nonmodel species, the zebra finch. Given the importance of …

The Impact Of Traumatic Brain Injury On Noradrenergic Innervation Of The Prefrontal Cortex, Jil P. Modi, Christopher P. Knapp, Rachel L. Navarra

Rowan-Virtua Research Day

Traumatic Brain Injury (TBI) is a common cause of death and disability in the United States, and it can occur due to varied reasons including motor vehicle accidents, gunshot wounds, and falls. Following TBIs, patients are often left with lifelong disabilities and cognitive problems that can lead to increased risk-taking behaviors. The main goal of my research was to understand the neural mechanisms that drive increased risk-taking behaviors due to TBIs. The specific areas of the brain I was interested in looking at were the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), and/or anterior cingulate cortex (ACC) of the prefrontal …

Pediatric Neurotropic Infection Alters Synaptic Development In The Developing Brain, Anuoluwapo Grace Fadare, Yashika S. Kamte, Manish N. Chandwani, Lauren A. O'Donnell

Rowan-Virtua Research Day

Many neurotropic viruses cause more significant pathology in younger hosts as their brains are still developing. This experiment asked how central nervous system (CNS) viral-infections affect the development of synapses in the pediatric brain during infection and post-infection. Synaptogenesis is at its peak in pediatric mice (10 days old) and we hypothesized that a neurotropic infection could disrupt synaptic proteins. We used a transgenic mouse model where measles virus (MV) infects only mature neurons, leading us to question whether synapses were impacted. We examined synaptic markers in the cerebellum and hippocampus in MV-infected and uninfected mice 9 days and 90 …

The Influence Of Bihemispheric Transcranial Direct Current Stimulation On Muscle Fatigue, Ananya Singh Chauhan

UNLV Theses, Dissertations, Professional Papers, and Capstones

Unilateral transcranial direct current stimulation (tDCS) using two electrodes placed over the primary motor cortex (M1) and the contralateral supraorbital (SO) region (M1-SO montage) has been shown to decrease the progression of muscle fatigue. The primary purpose was to determine the impact of bihemispheric tDCS (bi-tDCS) applied over the left and right M1s (bi-tDCS) on the time to task failure (TTF) of a precision-grip task. The study implemented a double-blind, randomized, SHAM-controlled, within-subjects design. A total of 20 participants performed two experimental sessions (bi-tDCS and SHAM conditions) separated by a one-week washout. During each experimental session, a fatiguing isometric contraction …

The Influence Of Bilateral Dual Source Transcranial Direct Current Stimulation On The Progression Of Muscle Fatigue, Eliza Clinton

UNLV Theses, Dissertations, Professional Papers, and Capstones

Transcranial direct current stimulation (tDCS) applied unilaterally to the primary motor cortex (M1) can significantly prolong the time to task failure (TTF) of a fatiguing contraction. The primary purpose of the study was to examine the influence of bilateral dual source tDCS (dstDCS) applied over the left and right M1s (ds-tDCS) on the TTF of a precision grip task. This was accomplished through the utilization of a double-blind, randomized, SHAM-controlled, within-subjects design. Fourteen participants completed two experiments (ds-tDCS and SHAM stimulation conditions) with a seven-day washout period between sessions. Each experiment involved the performance of a sustained isometric fatiguing contraction …

The Feasibility Of High-Intensity Training To Improve Self-Control And Occupational Participation In At-Risk Adolescents, Tashia Kaplan

UNLV Theses, Dissertations, Professional Papers, and Capstones

Purpose

Adolescence is a challenging time navigating self-control and decision-making, creating vulnerability to developing poor habits and unhealthy behaviors. This feasibility study aimed to determine if a high-intensity training program (HIT) would improve self-control, health-related behaviors, and healthy occupational participation in at-risk adolescents in the Real Talk Youth Impact Program (Real Talk), measured by the Occupational Experience Profile (OEP).

Methodology

Three at-risk adolescent were recruited via convenience sampling from Real Talk to participate in a twelve-session HIT intervention, one participant completed all sessions. Researchers used a quasi-experimental exploratory sequential mixed-methods design to examine self-control, health-related behaviors, and occupational participation measured …

Investigations Into The Relationship Between Menopause And Alzheimer’S Disease Pathology In A Mouse Model With Ovarian Follicle Depletion, Amanda M. Leisgang Osse

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer’s Disease (AD) currently affects about 6.9 million Americans, with over two-thirds of those individuals being women. Interestingly, changes in the brain indicative of AD coincide with the onset of menopause. Post-menopausal women have significantly higher levels of AD pathologies, including amyloid beta and hyperphosphorylated tau, than pre-menopausal women. To investigate the relationship between AD pathologies and menopause, we induced menopause-like state in an AD mouse model, APP/PS1, by treatment with 4-vinylcyclohexene diepoxide (VCD) to accelerate ovarian follicle depletion. To monitor the transition to menopause, vaginal lavages and cytology was performed to determine if mice reached anestrous. Both female APP/PS1 …

A Low Dose Of Electro-Psychedelic Treatment Increases Neuronal Dendritic Arborization And Filopodic Spine Density, Elaine Aquino Vasquez

UNLV Theses, Dissertations, Professional Papers, and Capstones

Neuropsychiatric disorders remain a formidable challenge to the global healthcare system, necessitating innovative treatments to address their complex pathophysiology. Alternative therapeutic approaches, including electroconvulsive treatment (ECT) and psychedelics, have gained attention for their capacity to relieve a broad range of symptoms. ECT is a long-standing effective therapy for patients, especially treatment-resistant ones. Psychedelics, like psilocybin, can induce profound and sustained therapeutic effects. The limited understanding of their mechanisms of action, compounded by the negative stigma surrounding ECT and psilocybin, prevents them from being used as adjunct agents. ECT and psilocybin promote synaptic plasticity and modulate neural remodeling, yet their comparative …