Neuroscience and Neurobiology 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 …

Determinants Of Corporal Punishment And Severe Physical Punishment In Egypt: A Mixed-Methods Analysis For Child Protection Policy, Marwa Moustafa Nassef

Theses and Dissertations

Corporal punishment (CP) and severe physical punishment (SPP) remain a major public health, child rights, and child protection policy concern. In Egypt, despite legislative reforms, survey-weighted analysis of the 2021 Egypt Family Health Survey (EFHS) 2021 (CAPMAS, 2022) reveals prevalence rates of 60.5% for CP and 27.4% for SPP among children aged 1–14 (author’s calculations using EFHS-2021, n=7623), yet evidence distinguishing the determinants of routine corporal punishment from escalation to severe physical punishment remains limited in low- and middle-income contexts. Guided by Bronfenbrenner’s ecological framework, this mixed-methods study identifies key drivers of CP and its escalation to SPP among Egyptian …

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 …

An Impact Assessment Of The Effectiveness Of Utilizing Informal Health Communication Interventions To Spread Health Recommendations And Change Public Perception, Lina Mohamed Ezzat Ahmed Abdel Mawgoud

Theses and Dissertations

Brain health is an increasingly urgent but critically under-addressed public health priority in Egypt and the wider MENA region. Despite its centrality to aging, productivity, and overall quality of life, public understanding of brain health remains limited, and stigma continues to shape responses to dementia and cognitive decline. This study evaluates the effectiveness of informal, culturally adapted health communication as a tool to shift perception, increase awareness, and promote behavior change among non-medically trained adults in Egypt.

Grounded in global evidence on cognitive reserve, neuroplasticity, and the life-course approach to brain health, the intervention translated expert-informed brain health recommendations into …

Building A Cell Specific System For In Vivo Rna Imaging Of The Endogenous Actin Gene In C. Elegans, Jasmine A. Huerta Canete

Theses and Dissertations

Messenger RNA (mRNA) plays a crucial role in protein synthesis and cellular processes, important for the development of cells such as neurons. When dysregulation occurs, it can lead to outcomes such as aberrant translation, causing neurodegenerative conditions to arise. Unfortunately, the localization of mRNA in an in vivo cell specific manner is still not understood. To address this, we decided to develop a cell-specific system to image RNA in vivo, within the organism known as C. elegans with a focus on the actin gene. The Actin gene encodes for an important cytoskeleton protein expressed ubiquitously, vital for the cell …

In Silico Investigations Of Class Ii Trans Activator (Ciita): Its Plausible Implications In Neuroinflammation And Neurological Disorders, Kishore N

Theses and Dissertations

Inflammation plays a significant role in maintaining homeostasis. Neuroinflammation is a chronic inflammatory response in the central nervous system (CNS), leading to brain or spinal cord dysfunction. To promote mental health, it is crucial to understand the regulation of neuroinflammation. Class II transactivator (CIITA) is a master-regulator of the major histocompatibility complex II (MHCII).

Modulation of CIITA has been suggested as a promising intervention for inflammatory conditions, including neurological disorders. However, there is limited knowledge about the role of CIITA and its interactors in inflammation. This study aimed to understand the role of CIITA in neuroinflammation and neurological disorders using …

Gardenia Jasminoides Extract As A Potential Neuroprotective Agent In An In Vitro Tauopathy Model, Inas Birekdar

Theses and Dissertations

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by the selective loss of neurons in various brain regions, leading to cognitive dysfunction. Neurofibrillary tangles (NFTs), composed of hyperphosphorylated tau protein accumulate within neuronal cells leading to cell death. The development of effective treatments for neurodegenerative diseases (NDs) remains a significant challenge, with neuroprotection emerging as a promising therapeutic strategy to slow disease progression and preserve cognitive function.

Objective: This study aims to investigate the potential neuroprotective effect of Gardenia jasminoides fruit extract, which contains geniposide, a biologically active compound known for its neuroprotective properties, in mitigating Tau hyperphosphorylation in …

The Role Of Cephalic Mechanosensory Bristles In Flight Initiation Of The Oleander Hawkmoth, Daphnis Nerii, Maitri Manjunath

Theses and Dissertations

During flight, insects sense air movement past their bodies via sensory bristles distributed all over their body. These bristles provide mechanosensory feedback to their nervous system, thereby modulating wing motion to cope with ambient wind conditions. In many insect systems including locusts, moths, etc., flight can be rapidly initiated by stimulating a set of bristles called cephalic bristles on their head. Rapid initiation of flight requires diverse, distributed flight-related reflexes to be simultaneously activated.

Thus, we hypothesized that cephalic bristles directly and simultaneously trigger diverse flight-related reflexes. We tested this hypothesis using the Oleander hawkmoth, Daphnis nerii, as our study …

Emotional Outbursts In Latinx Autistic Youth With Intact Or Non-Intact Families; Frequency, Severity, And Socio-Demographic Correlates, Sandra Lucia Masso Hernandez

Theses and Dissertations

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction, communication, and restricted repetitive behaviors. One of the core difficulties in individuals with ASD is related to emotional outbursts. Emotional outbursts (EO) are behavioral episodes in response to situations, environmental and physiological stimuli that occur in an extreme, unpleasant, sometimes aggressive way, often disproportionate to the context. Considering the impacts that EO’s can cause in populations with neurodevelopmental disorders and on the well-being and mental health of parents/caregivers, the need arises to evaluate these populations. Due to the core characteristics of ASD (such as a rigid mentality, …

Neurophysiological Indices Of Lexical Tone Processing In Children With Different Language Background, Andres Felipe Diaz

Theses and Dissertations

The development of lexical tone processing in children is shaped by both language experience and acoustic salience. While mismatch responses (MMRs) and late negativity (LN) components of event-related potentials (ERPs) have revealed early sensitivity to lexical tone in monolingual children, the timeline for achieving adult-like neural responses—particularly for acoustically distinct versus subtle tone contrasts— remains unclear. Moreover, little is known about how bilingual language experience, especially with tonal versus non-tonal home languages, modulates this neural processing. This study employed a passive multi-oddball paradigm using Mandarin Tone 3 (low dipping) as the standard, and Tone 1 (high level) and Tone 2 …

Investigating The Antibacterial And Immunomodulatory Effects Of Resolvin D2 On Monocytes And Macrophages, Cristina Maria Padovani

Theses and Dissertations

In the late phase of sepsis, immunosuppression occurs, where the host is unable to clear the pre-existing infection and is susceptible to secondary infections. It is believed that the ideal treatments for sepsis should attenuate immunosuppression so that the host can get back to homeostasis. Specialized Pro-resolving Mediators (SPMs) are endogenously- produced fatty acids that resolve infectious inflammation without being immunosuppressive. We hypothesize that an SPM – Resolvin D2 (RvD2) – can augment exhausted macrophage function during the immunosuppressive phase of sepsis. We developed a two-hit model to establish macrophage exhaustion in vitro, and found that RvD2 increased NF-κB activity, …

Pipecolic Acid And Novel Insights Into Cerebral Malaria, Akua E. Mensah

Theses and Dissertations

Cerebral malaria (CM), a severe manifestation of Plasmodium infection, prompts our investigation into the nuanced role of pipecolic acid in its pathophysiology. To unravel the molecular intricacies, we conducted in vitro lysine labeling techniques of mice infected with P. berghei ANKA parasites, and human P. falciparum grown in vitro, aiming to discern the impact of Plasmodium on pipecolic acid production. Previous observations indicated an elevation in pipecolic acid levels correlating with neurological decline in children with CM. In our study, confirming elevated pipecolic acid presence in the plasma and brain tissues of CM patients and the animal model of CM, …

Exploring A Gene Panel For Parkinson’S Disease In An Egyptian Cohort, Asmaa Saeed Gabr

Theses and Dissertations

Parkinson’s disease is a highly heterogeneous disorder characterized by diverse neuropathological features, clinical presentations and progression patterns. In Egypt, Parkinson’s disease incidence rates lie outside the range reported elsewhere. The genetic background to the pathogenesis of Parkinson's disease has been postulated for a long time. However, Parkinson’s disease has never been systematically investigated in Egypt. This study aimed to explore genetic variants and interactions that are associated with the familial and sporadic forms of Parkinson's disease in an Egyptian cohort. This includes examining variants in PD-related genes, exploring the role of specific genes like MAPT and adjacent genomic regions, and …

The Relationship Between Cognitive Impairment In Psychiatric Patients And Readmission Rate To An Inpatient Facility, Cherilyn Isis Schuff

Theses and Dissertations

The primary intention of this study was to further understand the impact of assessing cognitive impairment in psychiatric patients, as a mediating factor on readmission rates. Mild cognitive dysfunction impacts a patient’s functional outcomes (Bowie & Harvey, 2006; Davis et al., 2012; Marcantonio, et al., 2001). Little information exists to guide best practices in the treatment of adults with cognitive impairment who are hospitalized for acute conditions (Davis et al., 2012). A cognitive impairment may impact patient prognosis and ability to function outside of a setting focused on stabilization. Neuropsychological testing is a valuable tool in predicting a patient’s cognitive …

Investigation Of Brain Function And Structural Development As Risk Factors Of Suicidal Thoughts And Behaviors, Yi Zhou

Theses and Dissertations

Background: Identifying risk factors for suicidal thoughts and behaviors, especially causal ones, will be imperative to improving screening and treatment interventions. To identify replicable brain-based risk factors, there is increasing evidence indicating the need for large sample sizes, in the hundreds to thousands, in order to achieve a sufficient level of statistical power to detect them. Furthermore, longitudinal studies of brain and behavioral factors will be essential to understanding how suicide develops, especially the transition from suicide ideation to attempt. While experimental studies may not be feasible or ethical, genetically informed methods for testing evidence for causation are an alternative …

Re-Programming Transcription Factor Function For Neuroscience Research Of Addiction: Investigating The Role Of Zinc Finger Proteins In Driving Cocaine Reinforcement In Mice, Joseph A. Picone

Theses and Dissertations

Administration of addictive drugs like cocaine or morphine initiates aberrant gene transcription within brain reward circuitry neurons, which contributes to the lasting behavioral maladaptations that define addiction. The drug-induced expression and function of key brain transcription factors (TFs) is one major mechanism through which these drugs are able to regulate transcription, and as a consequence, lasting damaging drug-related behaviors including compulsive drug use. The goal of this dissertation is to more fully understand the molecular mechanistic drug-specific actions of TFs within the rodent nucleus accumbens (NAc). The findings from these studies could serve as the basis to identify novel candidate …

Nanoscale Modeling Of Membrane Systems Under Mechanical Deformation In Traumatic Brain Injury Using Molecular Dynamics, Anh Thi Ngoc Vo

Theses and Dissertations

Neuronal membrane disruption and mechanoporation are nanoscale damage mechanisms that critically affect brain cell viability during traumatic brain injury (TBI). These nanoscale cellular impairments are elusive in experiments and necessitate in silico approaches such as molecular dynamics (MD) simulations. Implementing MD, this research aims to investigate the effects of different key factors related to membrane deformation and damage, including force field resolutions, lipid compositions, and loading conditions.

To examine the impact of force field resolution, MD deformation simulations were conducted on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) lipid bilayer membranes, using all-atom (AA), united-atom (UA), and coarse-grained Martini (CG-M) force fields. The mechanical responses …

Neuroprotective Effects Of Green Tea (Camellia Sinensis) And Broccoli (Brassica Oleracea) Extracts In An In Vitro Model Of Multiple Sclerosis, Sara Taha Fathallah

Theses and Dissertations

Multiple Sclerosis (MS) is a neurodegenerative autoimmune disease in which the immune system attacks the central nervous system (CNS) resulting in demyelination. Currently, there is no specific treatment for MS. Here, we propose testing the neuroprotective potential of Green tea (Camellia sinensis), and Broccoli (Brassica oleracea) extracts in an in vitro model of multiple sclerosis.

Methods and Results: Green tea and Broccoli plant extracts were analyzed with GC-MS and tested for their neuroprotective effects in an in vitro MS model using Cuprizone (CPZ) on the Human neuroblastoma SH-SY5Y cell line. Cell viability assays proved the safety of the extracts …

Effects Of Hiv-1 Tat And Opiates On Gene Regulation Of Oligodendrocyte Lineage Cells: Identification Of Myrf As A Novel Target, Kelly M. Flounlacker

Theses and Dissertations

HIV-associated neurocognitive disorders remain pervasive even with increased efficacy/use of antiretroviral therapies. Opioid use/abuse among HIV+ individuals is documented to exacerbate deficits. White matter (WM) alterations (myelin pallor, volume/structural) detected by diffusion tensor imaging, are common observations in HIV+ individuals. Using transgenic mice expressing HIV-1 Tat, we examined effects of 2-6 weeks of Tat/morphine exposure on WM using genomic/biochemical methods. RNA sequencing of striatal tissue after 2-weeks revealed robust changes in mRNAs associated with oligodendrocyte populations/myelin integrity, including Transferrin, Ndrg1, and myelin regulatory factor (Myrf/Mrf), an oligodendrocyte-specific transcription factor involved in differentiation/maturation. Immunoblots conducted after 6-weeks exposure in …

Interactions Between Hiv And Opioids On Antiretroviral Accumulation, The Blood Brain Barrier, And The Inflammatory Response In The Brain., Kara Rademeyer

Theses and Dissertations

The complex mechanisms related to HIV infection, neurodegeneration, and chronic neuroinflammation collectively describe neuroHIV (Hauser et al. 2007; Chang et al. 2014; Smith et al. 2014). Specifically, opioid abuse, poor penetration of antiretroviral (ARV) drugs, chronic inflammation and neuronal injury/degeneration are all implicated in neuroHIV (Fantuzzi et al. 2003; Letendre et al. 2004; Verani et al. 2005; Duncan and Sattentau 2011; Hong and Banks 2015; Simoes and Justino 2015; Olivier et al. 2018; Murphy et al. 2019; Osborne et al. 2020). For the first time, we demonstrate that morphine, fentanyl, and methadone in vivo alter the brain accumulation of ARVs, …

Unraveling The Consequence Of Adult Onset Sulfatide Depletion: Its Implications In Myelin And Axonal Heath In The Context Of Neurodegenerative Disease, Elizabeth Dustin

Theses and Dissertations

Multiple Sclerosis is an immune mediated disease of the CNS. MS is diagnosed through detection of demyelinated regions. However, recent studies demonstrate that Normal Appearing White Matter (NAWM) contains substantial pathology. One such pathology observed in the NAWM is the reduction of sulfatide. The proper stoichiometry of lipids in myelin acts to maintain rapid conduction velocity, provide trophic support to the neuron, and protect the axon from degeneration. We previously characterized a mouse lacking sulfatide’s synthesizing enzyme, CST through constitutive gene disruption and demonstrate that sulfide is required for proper stability of the myelin sheath. However, since MS is typically …

Epithelial Membrane Protein 3 (Emp3b) Is A Novel Regulator Of Sympathetic Nervous System Development In Zebrafish., Jessica M. White

Theses and Dissertations

Notable progress has been made in understanding the development of the neural crest (NC). Neural crest cells (NCCs) can be divided into 4-5 subpopulations. A major lineage among trunk NC derivatives are sympathoadrenal (SA) cells, which give rise to the sympathetic nervous system (SNS). Trunk NCCs follow a ventromedial migration pathway where signals derived from the dorsal aorta instruct migrating NCCs to a SA cell fate. Defects in NC development can result in syndromes known as neurocristopathies. Neuroblastoma is one of the most common forms of pediatric cancer affecting nearly 800 infants each year in the United States (Takita et …

The Impact Of Hiv-1 Tat And Morphine On Spatial Distribution Of Drugs In The Brain., Austin M. Jones

Theses and Dissertations

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, the central nervous system (CNS) remains affected by the virus. Approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND) or neuroHIV. Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, viral replication, and potentially altering the antiretroviral concentrations within the brain.

Using a transgenic mouse that expresses the HIV-1 Tat protein, we examined the effects of Tat and morphine on antiretroviral accumulation and distribution and the effects of Tat on morphine accumulation within the brain using infrared matrix-assisted laser desorption electrospray ionization with mass spectrometry imaging (IR-MALDESI-MSI). …

Mechanistic Insight Into Traumatic Brain Injury Induced Neuronal Membrane Disruption: Cathepsin B Relocalization And A Neun Negative Cortical Neuron Subpopulation, Martina L. Hernandez

Theses and Dissertations

Traumatic brain injury (TBI) is a mechanical insult to the head that leads to brain damage and, in turn, causes long-term sensory, motor, cognitive, and affective dysfunction. Diffuse pathologies seen following such injury are associated with these life-altering outcomes that impact the daily lives of TBI survivors. The diffuse pathology that this body of work focuses on is neuronal membrane disruption; it is characterized by increased permeability of the neuron’s plasma membrane. Moreover, our lab had previously found that membrane disruption is exacerbated with intracranial pressure (ICP) elevation. We set out to measure the duration of membrane disruption following injury …

Unraveling The Anti-Inflammatory Mechanisms And Efficacy Of Cannabidiol On The Progression Of A Murine Model Of Multiple Sclerosis From The Innate To The Adaptive Immune System To Clinical Symptoms, Christa Marie Frodella

Theses and Dissertations

Cannabidiol (CBD), a non-psychotropic phytocannabinoid with structural similarity to Δ 9 -tetrahydrocannabinol (THC), is currently being investigated as a therapeutic for its immunosuppressive effects. One disease for which CBD is extensively researched is multiple sclerosis (MS), a demyelinating, autoimmune disorder, and its murine model counterpart, experimental autoimmune encephalomyelitis (EAE). The focus of this dissertation aimed to analyze the transcriptomic brain pathways in EAE and its comparison to MS in addition to CBD’s immunosuppressive mechanisms in the innate and adaptive immune systems. Evidence presented here showed that transcriptomic signaling pathways in the EAE brain of mice with clinical symptoms were similar …

Behavioral And Histological Inflammatory Analysis Of A Single, Mild Traumatic Brain Injury And Repeated Subconcussive Brain Injury Using A Rodent Model., Anna Marie Clay

Theses and Dissertations

Subconcussive (SC) impacts have become a growing concern within the neuroscience community regarding the immediate and long-lasting effects of sports-related injuries. While a single low-level impact, i.e., a subconcussion, may not cause cerebral perturbations, it has been increasingly recognized that repeated SC exposure can induce deleterious effects. Therefore, determining the lower limits of systematic perturbation resulting from multiple SC impacts is of critical importance in expanding our understanding of cerebral vulnerability and recovery. Currently, there is a lack of correlation between a mild traumatic brain injury (mTBI) and repeated SC impacts with respect to injury biomechanics. Moreover, the cumulative threshold …

Maternal Nutrient Restriction And Melatonin Supplementation Alter Neurotransmitter Pathways In Bovine Fetal And Placental Tissues, Allison R. Harman

Theses and Dissertations

Nutrient restriction is a relatively common production insult to pregnancy in cattle. Recently, melatonin supplementation has been investigated as a possible therapeutic to rescue the negative effects of nutrient restriction. Neurotransmitters have been implicated as having negative programming effects in mouse and human pregnancies, manifested as metabolic and neurologic disorders. The role of neurotransmitters in fetal development has only begun to be understood in mice and humans. Neurotransmitters have not been analyzed in cattle, much less within the context of a compromised pregnancy. Brangus heifers were allotted to one of four treatments (ADQ-CON, RES-CON, ADQ-MEL, RES-MEL) in either Fall 2019 …

Mirnas Levels In A Streptozocin Model Of Alzheimer’S Disease, Nada Moustafa

Theses and Dissertations

Dementia entails a progressive decrease in cognitive functions, with 50%-75% of cases attributed to Alzheimer’s disease (AD); an aging-associated condition characterized by the build-up of tangled phosphorylated Tau (p-Tau) protein and beta-amyloid (Aβ) depositions. Sporadic AD (sAD) is multifactorial in nature, resulting from a combination of environmental and genetic predisposing factors. Type 2 diabetes mellitus (T2DM) is a leading risk factor for dementia, and deregulation of brain glucose metabolism is associated with early cognitive affection in sAD. Thus, the diabetogenic agent Streptozotocin (STZ) is used to experimentally create an AD model in animals (STZ-induced sAD), in which abnormalities in cerebral …

Individual Differences In Structure Learning, Philip Newlin

Theses and Dissertations

Humans have a tendency to impute structure spontaneously even in simple learning tasks, however the way they approach structure learning can vary drastically. The present study sought to determine why individuals learn structure differently. One hypothesized explanation for differences in structure learning is individual differences in cognitive control. Cognitive control allows individuals to maintain representations of a task and may interact with reinforcement learning systems. It was expected that individual differences in propensity to apply cognitive control, which shares component processes with hierarchical reinforcement learning, may explain how individuals learn structure differently in a simple structure learning task. Results showed …