Neuroscience and Neurobiology Commons^™

Oxidative Stress Mediated Glutamate Release And Nmda Receptor-Dependent Synaptic Remodeling In Radiation-Induced Cognitive Dysfunction, Thanh Lam

Dissertations and Theses (Open Access)

In children younger than 14 years old, the brain and other parts of the central nervous system are the most common sites for solid tumors. Radiotherapy is an effective treatment for central nervous system (CNS) tumors. However, it often causes a progressive decline in cognitive functions, which is especially devastating for pediatric patients. Although post-mitotic neurons are generally considered resistant to radiation-induced immediate cell death, ionizing radiation causes complex neurochemical and structural changes that damage synaptic integrity. In this study, we examined the molecular cascades following a 10 Gy radiation dose applied to mouse cortical neurons. We found that radiation-induced …

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 …

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 …

Investigation Of Environmental Influences On Multiple Sclerosis: A Study For Egypt’S Health, Noha Ezzaldin Alziny Ali

Theses and Dissertations

Background: Multiple sclerosis (MS) is a complex, chronic neuroinflammatory disease influenced by both genetic and environmental factors. While global research has identified potential environmental influences, most evidence comes from Western populations, creating a significant knowledge gap for regions like Egypt, which has witnessed a dramatic rise in MS prevalence over recent decades. This study hypothesized that Egyptian MS patients exhibit a distinct biological signature in their blood, characterized by an imbalance in essential and toxic trace elements (the metallome) and alterations in stress-response biomarkers associated with neuroaxonal injury and cellular stress. Objective: This study aimed to comprehensively profile and compare …

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 …

Stromal Interaction Molecule (Stim) Proteins In Microglia And The Impact On Store-Operated Calcium Entry (Soce) And Spinal Cord Injury Recovery, Norah G. Hill

College of Arts & Sciences Senior Theses

In spinal cord injury (SCI), worsening functional outcomes are largely because of secondary injury processes and prolonged chronic inflammation. A major contributor of secondary injury is overload of intracellular calcium, causing neuronal overexcitation and persistent inflammatory responses. One of the primary mediators of calcium entry into the cell is store-operated calcium entry (SOCE). In SOCE, sensors detecting calcium depletion from the endoplasmic reticulum stores are called STIM proteins (1-2). When calcium is low in the cell, STIM proteins will activate Orai channels to open, allowing for the influx of calcium into the cell. The purpose of this study was to …

Using A Toxic Aging Coin To Assess Hexavalent Chromium Neurotoxicity: Impact Of Cr(Vi) On The Blood-Brain Barrier, Liam Buchanan

College of Arts & Sciences Senior Theses

The US population faces simultaneous public health threats from both aging and environmental pollutants. Chief among these is hexavalent chromium [Cr(VI)], whose toxic effects in peripheral tissues are well-established but its effects on the brain are still understudied. Following previous results indicating hippocampal metals dyshomeostasis after Cr(VI) exposure, we aim to assess Cr(VI)’s impact on the blood-brain barrier (BBB), a key structure for brain protection. We exposed young, middle-aged, and geriatric rats of both sexes to low levels of Cr(VI) in their drinking water for 90 days, after which we used immunofluorescence and confocal microscopy to analyze tissues for evidence …

Revised - The Role Of Gad67/65 In The Therapeutic Effects Of Ketamine And Fluoxetine In Fear-Conditioned Mice, Alex G. Ottimer

All NMU Master's Theses

Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder and the most common disorder following exposure to a traumatic event. The most commonly used drugs in PTSD treatment are selective serotonin reuptake inhibitors (SSRIs), though only about 50% of patients respond to this treatment. Previous work in our lab demonstrated the combination of chronic fluoxetine (FLX) and acute ketamine treatment decreased fear response in a contextual fear paradigm in male C57/BL mice. In rodents, fear conditioning (FC) is commonly used in the literature to induce behaviors related to PTSD. The mammalian central fear memory circuit involves a dynamic interplay between …

Preclinical Animal Modeling To Investigate Redox-Mediated Molecular Dysfunction In Traumatic Brain Injury, Brandon Z. Mcdonald

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

Impacts associated with traumatic brain injury (TBI) induce a multitude of neurological morbidities mediated by a spread of biochemical dysfunction. Redox stress is a significant contributor to TBI pathophysiology and several redox stress markers have substantial evidence to support their role in diagnosing preclinical and clinical TBI. However, there is a critical need to verify their translational utility through correlations with behavioral, imaging, and molecular modalities. In chapter two, we examined the therapeutic efficacy of an antioxidant treatment (NPC3) using a controlled cortical impact (CCI) mouse model of TBI. NPC3 alleviated glial expression and reactivity while influencing the expression of …

Adventitial Macrophage Accumulation Impairs Perivascular Nerve Function In Mesenteric Arteries With Inflammatory Bowel Disease, Elizabeth A. Grunz, Benjamin W. Jones, Olubodun Michael Lateef, Sidharth Sen, Katie Wilkinson, Trupti Joshi, Erika M. Boerman

Biomedical Sciences

Introduction: Inflammatory bowel disease involves aberrant immune responses and is associated with both cardiovascular disease risk and altered intestinal blood flow. However, little is known about how inflammatory bowel disease affects regulation of perivascular nerves that mediate blood flow. Previous work found perivascular nerve function is impaired in mesenteric arteries with Inflammatory bowel disease. The purpose of this study was to determine the mechanism of impaired perivascular nerve function.

Methods: RNA sequencing was performed on mesenteric arteries from IL10−/− mice treated with H. hepaticus to induce disease (inflammatory bowel disease) or left non-gavaged (Control). For all other studies, Control and …

Effects Of Limb Dominance On Dopaminergic Neurodegeneration In A 6-Ohda Rat Model Of Parkinson’S Disease Assessed By Immunoblotting, Jasin Aziz Porshia, Deanna Chaialee, Dipesh Pokharel, Kala Venkiteswaran, Thyagarajan Subramanian, Dilshan Beligala

ONU Student Research Colloquium

Effects of Limb Dominance on Dopaminergic Neurodegeneration in a 6-OHDA Rat Model of Parkinson’s Disease Assessed by Immunoblotting

Jasin Porshia^a , Deanna Chaialee^a , Dipesh Pokharel^b,c , Kala Venkiteswaran^{b, c, d} , Thyagarajan Subramanian^{b, c, d}, Dilshan Beligala^a

^aDepartment of Biological Sciences, Ohio Northern University, Ada, OH, USA

^bDepartment of Neurosciences and Psychiatry, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

^cDepartment of Neurology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

^dDepartment of Neurology, Howard University, Washington, DC, …

Establishment Of A Hek293t Cell Model System To Investigate Direct Intracellular Interactions Between Amyloid-Β (Aβ) And The Nlrp3 Inflammasome, Cristina Sinobas Pereira

Dissertations

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide. While Amyloid-β (Aβ) aggregation is a defining pathological feature, increasing evidence highlights chronic neuroinflammation as a critical contributor to disease progression. Soluble Aβ assemblies can act as damage associated molecular patterns (DAMPs) including activation of the NLRP3 inflammasome, which links amyloid pathology to sustained inflammatory responses in the brain (Heneka et al., 2015; Nakanishi et al., 2018). However, the molecular mechanisms by which specific Aβ conformations influence inflammasome assembly remain incompletely understood.This study aimed to investigate whether distinct aggregation states of amyloid β42 (Aβ42) are …

Amyloid Beta-42 Neurotoxicity In Drosophila Retinal Development, Shay O. Sims, Pierce Duncan, Malachi Abon, Jacob G. Smith

Create@State

Alzheimer's disease (AD) represents one of the most prevalent neurodegenerative disorders globally. Thus far, the underlying mechanisms associated with the pathogenesis of AD are innately elusive. Two hallmarks associated with the progression of AD exist, including Amyloid-Beta 42 (Aβ42) protein plaque formation and hyperphosphorylation of tau proteins in neurons. Amyloid-beta is known to concentrate with other neuronal proteins as complexes form, including the cytoskeletal protein actin. However, whether actin contributes to neuronal decline in AD is unknown. To further understand the cellular cascades associated with AD, we investigated the role of cytoskeleton dynamics in modulating oxidative stress and neuroinflammation within …

Relish As A Temporal Switch In Neurodegeneration Using Drosophila Melanogaster, Kyle M. Johnson

Create@State

Neurodegenerative diseases are often linked to chronic inflammation in the nervous system, but it is still unclear what triggers this process during the early stages of disease. This project examines whether activation of the NF-κB transcription factor Relish may act as a temporal switch that contributes to early neurodegenerative stress in Drosophila melanogaster. As a result of many innate immune pathways are consistent between flies and humans, Drosophila serves as a useful model for studying how immune signaling affects neuronal health. In this study, neural driver lines were crossed with control strains to evaluate how changes in Relish signaling …

An Investigation Into Relish Activation As A Temporal Switch In Neurodegeneration, Kyle M. Johnson

Create@State

Neurodegenerative diseases are often linked to chronic inflammation in the nervous system, but it is still unclear what triggers this process during the early stages of disease. This project examines whether activation of the NF-κB transcription factor Relish may act as a temporal switch that contributes to early neurodegenerative stress in Drosophila melanogaster. As a result of many innate immune pathways are consistent between flies and humans, Drosophila serves as a useful model for studying how immune signaling affects neuronal health. In this study, neural driver lines were crossed with control strains to evaluate how changes in Relish signaling …

The Role Of Pten Subcellular Localization In Neuronal Development And Autism Spectrum Disorder, Nicole Desmet

Dartmouth College Ph.D Dissertations

Autism spectrum disorders (ASD) are genetically heterogeneous neurodevelopmental conditions that nevertheless converge on altered neuronal connectivity and circuit function. A central unresolved problem in the field is how diverse genetic perturbations, acting at different biological levels and developmental stages, give rise to shared neurodevelopmental outcomes. This dissertation addresses this problem by examining how gene function, subcellular signaling, and developmental context interact to shape neuronal morphology and circuit-relevant phenotypes.

Cell-autonomous mechanisms regulating neuronal morphology are examined through the ASD risk gene Phosphatase and Tensin Homolog (PTEN) in developing dentate gyrus granule neurons. Selective biasing of PTEN to defined intracellular compartments in …

Survivin And Caspases Coordinate Proteolytic Cleavage Of The Saga Chromatin Modifying Complex, Elinor Harrison, Alejandro Damian, Cj Talton

Medical Student Research Symposium

Title: Survivin and Caspases Coordinate Proteolytic Cleavage of the SAGA Chromatin Modifying Complex

Elinor Harrison¹, Alejandro Damian¹, CJ Talton¹, Jelly H Soffers¹, Abudu I Bello¹, Kara M Costanzo¹, Joe Bean¹, Ryan D Mohan¹

¹Wayne State University School of Medicine

Background: The Spt Ada Gcn5 Acetyltransferase (SAGA) chromatin modifying complex is a critical regulator of gene expression. Mutation or stoichiometric imbalance of SAGA subunits leads to a spectrum of diseases in model organisms and in humans, including neurodegeneration. SAGA contributes to gene activation through coordinated …

Hsp90 Inhibitor In Reducing Integrated Stress Response In An Experimental Mouse Model Of Spinal Cord Injury, Yousef Abozaid, Aditya Sarkar, Lukasz P. Slomnicki, Michal Hetman

The Cardinal Edge

Spinal cord injury (SCI) initiates a complex cascade of molecular events, including protein misfolding and neuroinflammation, contributing to neural damage and impaired functional recovery. Heat Shock Protein 90 (HSP90), a critical molecular chaperone involved in cellular stress responses, emerges as a promising therapeutic target to mitigate secondary damage after SCI. This study was designed to validate the in-vivo effects of different doses of HSP90 inhibitor, HSP990-i, administered acutely after moderate T9 SCI mouse model. The level of HSP70 protein level is measured through western blot from the injury epicenter. Adult mice underwent experimental contusive SCI at the T9 level, followed …

Disrupted Nuclear Function And Nucleocytoplasmic Transport In Parkinson’S Disease, Ichiro M. Matoba

The Cardinal Edge

No abstract provided.

Situation Mouse All Floxed Up: Exploring Phenotypic Abnormalities In Bdnf Floxed Mice, Marissa A. Burkman

All NMU Master's Theses

Animal research is a contentious topic in both the scientific and general communities.  It is essential that our animal models accurately and predictably depict intended phenotypes, necessitating careful colony monitoring and maintenance.  Volunteer animal staff in the Ottem Laboratory became concerned when mice with LoxP sites flanking the BDNF gene depicted anxiety-like behaviors such as aggression, difficulty handling, and increased agitation.  Though many studies have noted behavioral and phenotypic abnormalities related to large gene inserts, few have noted abnormalities with small gene inserts such as the 34 bp LoxP site.  Brandt (2018) performed a three-stage behavioral protocol on these mice …

Obesity Does Not Significantly Impact Clinical Outcomes Following Anterior Cervical Discectomy And Fusion, Ishan Shah, Alejandro Perez-Albela, Riya Shah, Charles Furlong, Puru Sadh, John Czerwein, Alan Daniels, Bryce A Basques

SKMC Student Presentations and Publications

BACKGROUND: With obesity rates rising among patients undergoing anterior cervical discectomy and fusion (ACDF) and more procedures shifting to outpatient settings, this study aimed to evaluate the impact of body mass index (BMI) on complications, sagittal alignment, and patient-reported outcomes (PROs).

METHODS: A prospectively maintained database of 302 patients who underwent ACDF for myelopathy or radiculopathy between 2020 and 2022 at a single academic center was analyzed. Patients were stratified into four BMI categories: normal (18.5-< 25), overweight (25-< 30), obese class I (30-< 35), and obese class II/III (≥35). Collected data included demographics, comorbidities, perioperative variables, radiographic measures (cSVA, Cobb angle, etc.), and PROs (VAS, NDI). Univariate regression compared demographics, alignment, and PROs, while multivariate analyses assessed complications and perioperative factors.

RESULTS: BMI was not independently associated with higher rates of postoperative complications, including adjacent segment disease, subsidence, reoperation, or other adverse events. Patients in …

Local Angiotensin Converting Enzyme 2 (Ace2) Enzymatic Activity Modulates Cholinergic Interneuron Function In The Dorsolateral Striatum, Aria R. Walls

Dissertations, Theses, and Capstone Projects

The renin angiotensin system (RAS) is an ancestrally ancient peptidergic signaling pathway best known for its role regulating blood pressure in the periphery. However, its presence and importance in the central nervous system has more recently been identified and is less well understood. Previous work shows RAS is expressed in the nigrostriatal pathway of the basal ganglia and has been implicated in basal ganglia disorders including Parkinson’s disease (PD) and levodopa-induced dyskinesia (LID). Interestingly, the canonical and noncanonical arms of the RAS pathway produce opposite effects on PD disease vulnerability and progression. The shift from the neurodegenerative canonical RAS to …

Silver Nanoparticle-Induced Disruption Of Astrocytic Morphology And Synaptic Microarchitecture In Rat Brain, Elli Williams

Theses, Dissertations and Capstones

Silver nanoparticles (AgNPs) are widely incorporated into consumer and medical products due to their antibacterial properties, increasing the potential for chronic exposure. AgNPs can be released into the environment, enter the body through ingestion or inhalation, cross the blood-brain barrier (BBB), and bioaccumulate in brain tissue. Previous in vitro studies demonstrate that AgNP exposure disrupts cytoskeletal organization and induces neurite collapse in neural cells, suggesting vulnerability of cytoskeleton-dependent structures in vivo. Astrocytes, through their perisynaptic astrocytic processes (PAPs) and perivascular endfeet, play critical roles in maintaining synaptic and neurovascular architecture, both of which rely heavily on cytoskeletal integrity. This …

Rna-Sequence-Driven Identification Of Differentially Expressed Genes In Α-Crystallin-Deficient Zebrafish, Kehlie Hopper

SPARK Symposium Presentations

Fetal Alcohol Syndrome (FAS) is a condition that develops in infants when exposed to alcohol in utero, leading to physical impairments such as reduced eye size and disrupted retinal function. Alpha-crystallin A is a key structural protein required for proper lens development and maintenance of transparency, while Alpha-crystallin B plays a protective role against cellular stress during eye development. In this study, I compared AB wild-type (ABWT), αA-crystallin knockout (cryaa), and αB-crystallin knockout (cryaba) zebrafish to investigate how the loss of these proteins influences eye development under ethanol exposure. The cryaa mutants exhibited reduced eye size even under control conditions, …

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, …

Design And Advancement Of Analytical Frameworks For In Vivo Single-Photon Calcium Imaging To Characterize Temporal- And Treatment-Dependent Neural Adaptations To Opioid Exposure And Withdrawal In The Medial Prefrontal Cortex, Alexia R. Alsum Dr.

Theses and Dissertations--Pharmacy

Despite the availability of several approved medications for opioid use disorder (OUD), it remains a significant public health concern characterized by persistent neurobiological adaptations that drive relapse and impede successful recovery. The medial prefrontal cortex (mPFC), a region critical for executive control and decision-making, undergoes pronounced functional changes during chronic opioid exposure and withdrawal, yet the cellular mechanisms underlying these adaptations remain poorly understood. This dissertation aims to investigate longitudinal alterations in mPFC neural activity across opioid exposure and withdrawal using in vivo single-photon calcium imaging and newly developed computational frameworks.

Following standard preprocessing to extract and normalize calcium traces, …

The Serotonin 1b Receptor In Psilocybin’S Therapeutic-Like Mechanisms: From Behavior To Network Reorganization, Sixtine Fleury

Dartmouth College Ph.D Dissertations

Mood disorders represent a substantial and growing global health crisis, with ~10 million adults in the US meeting criteria for a major depressive disorder (MDD). Current first-line treatments such as SSRIs require long-term daily administration and fail a significant proportion of patients, driving renewed interest in rapid-acting alternatives. Psilocybin, a serotonergic psychedelic, shows growing clinical evidence of efficacy in treating depressive and anxiety disorders, often producing therapeutic effects persisting weeks to months following a single dose. Yet, the neural mechanisms underlying these enduring effects remain poorly understood and have been largely attributed to the serotonin 2A receptor (5-HT2AR) based on …

The Effects Of Stress-Related Hormones On Excitatory Synapse Formation, Autumn C. Garvey

Honors Undergraduate Theses

Stress profoundly influences brain function through neuromodulatory hormones that regulate synaptic plasticity, yet how temporal patterns of hormone exposure shape excitatory synapse formation remains poorly understood. This study investigates how exposure to stress hormones, norepinephrine and cortisol, affects excitatory synapse development. While existing research primarily compares concentration models, real-world stress occurs in variable patterns that may produce distinct neural outcomes. To address this gap, differentiated Neuro2A neuronal cells are exposed to norepinephrine or cortisol under a continuous treatment paradigm designed to model chronic stress conditions. Following treatment, immunofluorescence imaging is utilized to quantify excitatory synapse formation through analysis of presynaptic …

Microglial Apoe Across Alzheimer’S Disease-Relevant Pathologies, Georgia Nolt

Theses and Dissertations--Physiology

APOE exists as three common alleles (APOE2, APOE3, APOE4) that encode their corresponding protein isoforms (apoE2, apoE3, apoE4). Despite differing by only one or two single-amino acid substitutions, each APOE allele confers a distinct AD risk profile with APOE4 increasing risk by 28% and APOE2 decreasing risk by 14% compared to the most commonly expressed APOE3 allele. While traditionally considered “neutral,” APOE3 still accounts for ~36% of AD cases while APOE4 contributes ~57%, indicating that the majority of AD cases would not occur in the absence of the APOE3 and APOE4 alleles. Microglia, the resident phagocytic immune cells …

Forcing A Molecule To Switch: Quantifying Mechanical Control At The Atomic Scale, A. M. Shashika D. Wijerathna, Markus Zirnheld, Michael L. Hildebrand, Myles Perry, Marjorie Cenese, Yuan Zhang

Physics Faculty Publications

Mechanically induced conformational switching at the single-molecule level represents a fundamental mechanism for molecular functionality, yet quantitative characterization of the underlying force and energy landscape remains limited. Here, we study individual TBrPP-Co(II) molecules on Au(111) using qPlus atomic force microscopy. By reconstructing interaction potentials from 3D Δf(x,y,z) data, we determine a threshold force of ∼96 ± 8 pN and a tip-induced switching interaction energy of ∼38 ± 4 meV associate with the conformational transition. The isolated tip-molecule force follows a power law (exponent ∼6), indicating dominance of long-range van der Waals interactions. …