Neuroscience and Neurobiology Commons^™

Azithromycin Reduces Hemoglobin-Induced Innate Neuroimmune Activation, Chirayu D. Pandya, Hemendra J. Vekaria, Miriam Zamorano, Amanda L. Trout, Rodney M. Ritzel, Gary Guzman, Christopher Bolden, Patrick G. Sullivan

Neurology Faculty Publications

Neonatal intraventricular hemorrhage (IVH) releases blood products into the lateral ventricles and brain parenchyma. There are currently no medical treatments for IVH and surgery is used to treat a delayed effect of IVH, post-hemorrhagic hydrocephalus. However, surgery is not a cure for intrinsic brain injury from IVH, and is performed in a subacute time frame. Like many neurological diseases and injuries, innate immune activation is implicated in the pathogenesis of IVH. Innate immune activation is a pharmaceutically targetable mechanism to reduce brain injury and post-hemorrhagic hydrocephalus after IVH. Here, we tested the macrolide antibiotic azithromycin, which has immunomodulatory properties, to …

The Biobehavioral Effects Of Embryonic Exposure To Neural Inflammation And Oxidative Stress In Zebrafish, Dalton J. Anderson

Honors College Theses

The purpose of this research is to improve understanding of the neurodevelopmental effects of embryonic exposure to elevated inflammation and oxidative stress induced by the antipyretic drug acetaminophen (APAP). Our study was the first to examine the interactive effects of APAP and inflammation in zebrafish embryos and how the treatments affect brain development and larval behavior. Experimental groups of zebrafish larvae were exposed to lipopolysaccharide (LPS) to induce inflammation, APAP, or LPS + APAP and larval behavior was analyzed using Ethovision automated behavioral tracking software. We also measured changes in whole-brain Glycogen Synthase Kinase 3 Beta (GSK3B) and GSK3B phosphorylation, …

Utilizing Ai Integrated Neuroimaging Technology To Expand Upon Machine Learning In Positron Emission Tomography Technology With The Aim Of Detecting Amyloid Beta Biomarkers Early In The Onset Of Alzheimer's., Ethan S. Terman

Undergraduate Research Posters

Early intervention in Alzheimer's is vital for treatment. The earlier a professional can detect symptoms and make a diagnosis the earlier a prognosis can be implemented. With the prevalence of data in our day-to-day world combined with Artificial intelligence (AI), utilizing both for machine learning can pave the way for more accurate and efficient detection of Alzheimer's and other neurodegenerative diseases. AI combined with Machine learning (ML) increases diagnostic efficiency and reduces human errors, making it a valuable resource for physicians and clinicians alike. With the increasing amount of data processing and image interpretation required, the ability to use AI …

Different Cohort, Disparate Results: Selection Bias Is A Key Factor In Autopsy Cohorts, Kathryn Gauthreaux, Walter A. Kukull, Karin B. Nelson, Charles Mock, Yen-Chi Chen, Kwun C. G. Chan, David W. Fardo, Yuriko Katsumata, Erin L. Abner, Peter T. Nelson

Neurology Faculty Publications

INTRODUCTION: Research-oriented autopsy cohorts provide critical insights into dementia pathobiology. However, different studies sometimes report disparate findings, partially because each study has its own recruitment biases. We hypothesized that a straightforward metric, related to the percentage of research volunteers cognitively normal at recruitment, would predict other inter-cohort differences.

METHODS: The National Alzheimer’s Coordinating Center (NACC) provided data on N = 7178 autopsied participants from 28 individual research centers. Research cohorts were grouped based on the proportion of participants with normal cognition at initial clinical visit.

RESULTS: Cohorts with more participants who were cognitively normal at recruitment contained more individuals who …

Cognitive Decline, Aβ Pathology, And Blood–Brain Barrier Function In Aged 5xfad Mice, Geetika Nehra, Sasivimon Promsan, Ruedeemars Yubolphan, Wijitra Chumboatong, Pornpun Vivithanaporn, Bryan J. Maloney, Anusorn Lungkaphin, Bjoern Bauer, Anika M. S. Hartz

Markey Cancer Center Faculty Publications

Background

Patients with Alzheimer’s disease (AD) develop blood–brain barrier dysfunction to varying degrees. How aging impacts Aβ pathology, blood–brain barrier function, and cognitive decline in AD remains largely unknown. In this study, we used 5xFAD mice to investigate changes in Aβ levels, barrier function, and cognitive decline over time.

Methods

5xFAD and wild-type (WT) mice were aged between 9.5 and 15.5 months and tested for spatial learning and reference memory with the Morris Water Maze (MWM). After behavior testing, mice were implanted with acute cranial windows and intravenously injected with fluorescent-labeled dextrans to assess their in vivo distribution in the …

Oxidative Stress Alters Mitochondrial Homeostasis In Isolated Brain Capillaries, Gopal V. Velmurugan, Hemendra J. Vekaria, Anika M. S. Hartz, Björn Bauer, William Brad Hubbard

Markey Cancer Center Faculty Publications

Background

Neurovascular deficits and blood-brain barrier (BBB) dysfunction are major hallmarks of brain trauma and neurodegenerative diseases. Oxidative stress is a prominent contributor to neurovascular unit (NVU) dysfunction and can propagate BBB disruption. Oxidative damage results in an imbalance of mitochondrial homeostasis, which can further drive functional impairment of brain capillaries. To this end, we developed a method to track mitochondrial-related changes after oxidative stress in the context of neurovascular pathophysiology as a critical endophenotype of neurodegenerative diseases.

Methods

To study brain capillary-specific mitochondrial function and dynamics in response to oxidative stress, we developed an ex vivo model in which …

Developmental Stress Signaling And Substance Use: Cortisol Reactivity Moderates The Effect Of Early Life Adversity On Alcohol Misuse Behaviors Among College Students, Keeley Lariviere

CMC Senior Theses

Stress-motivated drinking is common among college students facing increased independence and novel stressors. Early life adversity (ELA) as well as individual variation in neuroendocrine stress signaling significantly increase risk for alcohol misuse. Research on the relationships between ELA and the physiological stress response system, suggest that a dampened stress response may mediate the relations between ELA and alcohol misuse. However, other research has suggested that rather than acting as mediator, stress reactivity may interact (moderate) the relations between ELA and alcohol misuse. This study examined the associations between ELA, cortisol reactivity to an acute stressor, and self-reported alcohol misuse in …

Neurodevelopmental Vulnerability To Gestational Ozone Exposure, Vishnupriya Alavala, Sarah E. Brent, Christopher G. Canal, Joseph Wang, Russell P. Hunter, Matthew J. Campen, Andrew K. Ottens

Undergraduate Research Posters

Ambient air pollution accounts for about 4.2 million premature deaths annually per the World Health Organization. Ozone (O3) is a highly reactive air pollutant found in smog and is implicated in cellular damage leading to organ dysfunction. Ambient air pollution is associated with neurodevelopmental, behavioral, and cognitive disorders though ozone’s role is unknown. Studies here look at ozone exposure shortly after implantation vs. shortly before term to evaluate differences in neurodevelopmental susceptibility over time.

To inquire on the effects of ozone on the fetal brain, pregnant Sprague-Dawley rats were exposed once to 0.3 ppm of O3 or filtered air (FA) …

Role Of The Anti-Viral Immune Response In Neural Cell Modulation And Neurological Sequelae Of Childhood Viral Infections, Yashika Kamte

Electronic Theses and Dissertations

Viral infections of the central nervous system (CNS) often result in neurological sequelae and are considered a risk factor for the development of neurological disease. Moreover, the outcomes of a viral infection are largely dependent on the age of the host, with younger hosts developing more profound neuropathology. Perhaps the developing brain coupled with an immature immune system contributes to worse outcomes in the very young. Children suffering from brain infections are more prone to develop enduring neurological impairments even after recovery from the infection. Although majority of the brain growth occurs in utero, neurodevelopment continues throughout the juvenile …

Proteasome Inhibition Protects Blood–Brain Barrier P-Glycoprotein And Lowers Aβ Brain Levels In An Alzheimer’S Disease Model, Milica Vulin, Yu Zhong, Bryan J. Maloney, Björn Bauer, Anika M. S. Hartz

Markey Cancer Center Faculty Publications

Background Loss of P-glycoprotein (P-gp) at the blood–brain barrier contributes to amyloid-β (Aβ) brain accumulation in Alzheimer’s disease (AD). Using transgenic human amyloid precursor protein (hAPP)-overexpressing mice (Tg2576), we previously showed that Aβ triggers P-gp loss by activating the ubiquitin–proteasome pathway, which leads to P-gp degradation. Furthermore, we showed that inhibiting the ubiquitin-activating enzyme (E1) prevents P-gp loss and lowers Aβ accumulation in the brain of hAPP mice. Based on these data, we hypothesized that repurposing the FDA-approved proteasome inhibitor, bortezomib (Velcade®; BTZ), protects blood–brain barrier P-gp from degradation in hAPP mice in vivo.

Methods We treated hAPP mice with …

The Eyes Beyond The Screen: Digital Media Policy And Child Health, Yahia Al-Qudah

Research Symposium

Background: Modern communication technology and digital media have provided society with a foundation for instant messaging. Pictures, videos, and texts connect individuals with families, friends, and the world. Consequently, digital media has accelerated exposure to risk in which children and adolescents are most vulnerable. This project’s objective is to 1) congregate and highlight current knowledge about the impact of digital media on child health, and 2) underline deficiencies in related laws and regulations as well as offer solutions in digital media policy.

Methods: A systematic literature review was conducted through the JAMA Pediatrics database with keywords such as “digital media,” …

Bisphenol-A And Phthalate Metabolism In Children With Neurodevelopmental Disorders, T Peter Stein, Margaret D Schluter, Robert A Steer, Xue Ming

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: The etiology of autism spectrum (ASD) and Attention Deficit/Hyperactivity (ADHD) disorders are multifactorial. Epidemiological studies have shown associations with environmental pollutants, such as plasticizers. This study focused on two of these compounds, the Bisphenol-A (BPA) and Diethylhexyl Phthalate (DEHP). The major pathway for BPA and DEHP excretion is via glucuronidation. Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine.

HYPOTHESIS: Detoxification of these two plasticizers is compromised in children with ASD and ADHD. Consequently, their tissues are more exposed to these two plasticizers.

METHODS: We measured the efficiency of glucuronidation in three groups of children, …

Changes In The Epigenetic Landscape Of Oligodendrocyte Progenitor Cells With Time, David K. Dansu

Dissertations, Theses, and Capstone Projects

Most neonatal oligodendrocyte progenitors (nOPCs) give rise to myelinating oligodendrocytes during development, while a proportion are retained as proliferative undifferentiated cells in the adult brain (aOPCs). Previous studies have reported distinct properties for those two populations but the molecular mechanisms underlying these intrinsic differences are not well understood. Using RNA-sequencing and unbiased histone proteomics analysis, we identify transcripts and histone marks that are higher in aOPCs than nOPCs. The genome-wide ChIP-sequencing analysis of chromatin from aOPCs compared to nOPCs detects greater occupancy of the H4K8ac mark at loci corresponding to the higher transcript levels of oligodendrocyte-specific transcription factors and lipid …

Brainwaves, Memory, And Reward, Rebecca Mccune

Dissertations, Theses, and Capstone Projects

The development of effective educational curricula for enhancing learning involves the crucial consideration of effort and rewards. In the realm of education, teachers commonly employ rewards as motivational tools. Traditionally, these rewards are given to students as a recognition of their successful performance. However, a thought-provoking idea emerges: What if we were to extend rewards to students not solely based on accurate answers, but also on the effort they invest, even in cases where their actual response might be incorrect? Our study explores the potential impact of this approach on the way information is absorbed and subsequently retained, specifically focusing …

Reviewing Research On Down Syndrome To Then Inform And Create A Children’S Book With A Child Protagonist Who Has Down Syndrome, Trey Williams

Honors Projects

Children's literature continually evolves, requiring a steadfast commitment to align with new insights into various disabilities for genuine and accurate portrayal. This project delves into leveraging research to craft a children's book featuring Bonnie Lynn, a protagonist with Down Syndrome, recognizing the growing presence of individuals with Down Syndrome in today's society and the imperative for empathetic understanding within this community.

Novel Insights Into Oligodendrocyte Biology From Developmental Myelination Studies In Autophagy Deficient Mice And Analysis Of Oligodendrocyte Translatome Response To Contusive Spinal Cord Injury., Michael David Forston

Electronic Theses and Dissertations

Loss of myelin causes severe neurological disorders and functional deficits in white matter injuries (WMI) such as traumatic spinal cord injury (SCI). This dissertation is focused on autophagy in OL development and the OL translatome after SCI. Chapter I describes the history of myelin, OL development, and their involvement in neurodegenerative diseases and SCI. The proteostasis network, in particular autophagy, and its contributions to white matter pathology is discussed. It concludes examining advantages and disadvantages of unbiased omics tools, like RiboTag, to study transcriptional/translational landscapes after SCI. Chapter II focuses on autophagy in OPC/OL differentiation, survival, and proper myelination in …

Analysis Of The Paraventricular Nucleus Of The Hypothalamus After Exposure To Decabromodiphenyl Ether In Mice, Tia Blossomgame, Hermei Herman, Sharlenn La, Jocelyn Saquisili, Annabella Vargas, Grace Martinichio, Vincent P. Markowski

McNair Scholars Program

No abstract provided.

Microglia Refine Early Multisensory Circuits In The Lateral Cortex Of The Inferior Colliculus In A Complement-Dependent Manner, Shaida Hamidi

Masters Theses, 2020-current

Microglia cells (MGCs), the resident macrophage of the brain, play a pivotal role in synaptic pruning of newly established circuits during early critical periods. Classical complement cascade signaling enables MGCs to identify unnecessary or underutilized contacts and specifically target them for removal and subsequent degradation. Such recognition and engulfment behaviors require receptor-ligand interactions, whereby “eat me” tags (complement component 3, C3) bind their cognate receptor (complement receptor 3, CR3) expressed on MGCs. Compromised complement signaling in certain systems results in under-pruning or unrefined map configurations, and is thought perhaps to underlie certain autism-related behavioral phenotypes (e.g. sensory hypersensitivities, decreased social …

Adolescents With Family History Of Alcohol-Use Disorders Have Reduced Structural Coherence Of Anterior Insula To Nucleus Accumbens Tract, Grace Wood

Psychological Science Undergraduate Honors Theses

Genetics play a significant role in predisposition towards alcohol use disorders. Analyzing the neural phenotypes related to alcohol use disorder development could allow researchers to predict one’s predisposition. The anterior insula (AIns) contributes to binge drinking tendencies while exhibiting downstream signaling towards the nucleus accumbens (NAcc). Recent research has examined this relationship simultaneously with alcohol consumption, but the genetic effect of the AIns and NAcc functional relationship prior to alcohol consumption has yet to be examined. In this study, we used data from the Adolescent Brain Cognitive Development (ABCD) study to analyze the structural coherence of the AIns to NAcc …

Early Life Stress Predicts Future Conduct Disorder In Adolescents, Savannah Ellis

Biological Sciences Undergraduate Honors Theses

Early Life Stress (ELS) and adversity increase people’s risk for developing mental, social, or emotional dysregulation and disorders later in life. The objective of this study was to test whether ELS in adolescents could prospectively predict future conduct disorder. The study additionally tested potential neural mediators of the effect of ELS on future conduct disorder, and specifically targeted the structural connections from the anterior insula and medial prefrontal cortex to the Nucleus Accumbens (NAcc). Data for the project came from the Adolescent Brain Cognitive Development Study (ABCD study), which is a longitudinal multi-site consortium funded by the National Institutes of …

Transcriptional Regulation Of Stem Cell Function In The Drosophila Central Nervous System, Amalia S. Parra

Biology ETDs

Development of multicellular organisms depends on coordination of various molecular mechanisms to ensure proper tissue size and structure. This is accomplished through intrinsic and extrinsic cues that regulate cell growth and proliferation both spatially and temporally. These well-coordinated signals are present from early developmental stages and remain active throughout development to ensure tissue structure is appropriate for function. This is particularly important in early cell types that form specialized lineages such as stem cells or those found throughout the body such as epithelia. While much progress has been made in understanding growth regulatory mechanisms, several fundamental aspects remain unknown. This …

Analysis Of Genes Responsible For Neuronal Morphological Changes In Down Syndrome Hipsc-Derived Neurons, Juhi Patel

Senior Theses

Down syndrome (DS) is a complex neurodevelopmental disorder caused by the trisomy of chromosome 21. DS is the largest genetic cause of intellectual disability, which occurs in varying severity among affected individuals. It is associated with a variety of developmental and cognitive defects, including reduced brain size, impaired synaptic function, and altered neuronal morphology. A number of genes have been identified to play critical roles in the development and maintenance of neuronal morphology, and alterations in the expression of some of these genes are implicated in the morphological changes observed in DS. Knocking out or altering their expression leads to …

P120-Catenin Subfamily Members Have Distinct As Well As Shared Effects On Dendrite Morphology During Neuron Development In Vitro, Maxsam Donta

Dissertations and Theses (Open Access)

Proper dendrite morphology is essential for neuronal connectivity and function, and abnormal dendrite morphology is seen in many neurological pathologies. This study characterizes and compares the effects of a group of four proteins – the p120-catenin subfamily – that regulate cytoskeletal remodeling and dendrite morphology. To do this, I tracked the endogenous localization of each p120-subfamily catenin during neuron development, and I determined how altering the expression of each p120-subfamily catenin affects dendrite morphology. I find that all catenins are expressed in dendritic processes and the soma, ARVCF-catenin is expressed at relatively high proportions in the nucleus, and p120-catenin and …

Recent Advances In The Role Of Rehabilitative Therapies For Parkinson’S Disease: A Literature Review, Bazza Sohail, Muhammad Affan Iqbal, Aisha Razzaq, Abdul Wasay Nafe, Robina Malik

Journal of Mind and Medical Sciences

Regardless of medical therapies and surgical interventions for Parkinson’s disease, patients develop progressive disability. The role of therapies is to maximize functional ability and minimize secondary complications through movement rehabilitation within a context of education and support for the whole person. The overall aim is to optimize independence, safety and wellbeing, thereby enhancing quality of life. Trials have shown that physiotherapy has short-term benefits in Parkinson’s disease. However, which physiotherapy intervention are most effective remains unclear. This article provides a guidance framework rather than a ’recipe’ for treatment. This review shows that a wide range of rehabilitative therapy interventions to …

The Genomics Of Autism-Related Genes Il1rapl1 And Il1rapl2: Insights Into Their Cortical Distribution, Cell-Type Specificity, And Developmental Trajectories, Jacob Weaver

MUSC Theses and Dissertations

Neuropsychiatric disorders have a significant impact on modern society. These disorders affect a large percentage of the population: schizophrenia has a world-wide prevalence of 1% and autism spectrum disorders (ASD) affects 1 in 59 school-aged children in the US. There is substantial evidence that most neuropsychiatric disorders have a genetic component. Thus, with the advent of high throughput sequencing much effort has gone into identifying genetic variants associated with these disorders. The emerging picture from these studies is a complex one where hundreds of genes with small effects interact with a varied landscape of common variants to result in disease. …

Consciousness, Evolution, And The Self-Organizing Brain, Karen Seymour

Journal of Conscious Evolution

While evolution is guided by natural selection, it is internally driven by self-organizing processes. The brain encompasses these complementary forces and dynamics of evolution in both its structure and dynamics by embodying a historical record of the factors that have shaped it throughout its evolutionary past, as well as by being shaped by selective parameters in real time. Self-organization is evident in not only the brain’s structure and form, but also in the processes that support consciousness. From the convergence of complex structure and the novelty-generating dynamics of chaos that both characterize the brain arises the experience of explicit consciousness, …

Effects Of Withania Somnifera On Zebrafish, Diyari Bekhtyar

Student Works

Withania somnifera (commonly known as Ashwagandha), is a plant in which its root powder is sold as a dietary supplement. It is being commonly used as an anti-anxiety supplement to combat stress. While the sale of Withania somnifera is widely accessible and available throughout the U.S., it is concerning that a number of teens and young adults are taking this supplement without consulting a physician. Previous studies and claims conclude that Withania somnifera has both neuroprotective and antiinflammatory properties in human neuronal cells. We have chosen to test Withania somnifera’s effects on early embryonic development using Danio rerio, zebrafish, as …

Gabaergic Interneurons And Prenatal Ethanol Exposure: From Development To Aging, Adelaide R. Tousley

Dartmouth College Ph.D Dissertations

Fetal Alcohol Spectrum Disorders are the most common non-genetic cause of neurodevelopmental disability worldwide. Individuals with Fetal Alcohol Spectrum Disorder experience clinical symptoms including differences in physical, cognitive and behavioral development beginning in early childhood, but continue to face challenges into adulthood. There is a critical need to examine the effects of prenatal ethanol exposure across early development, and to establish how the developmental effects of prenatal ethanol exposure may or may not progress in aging individuals. To contribute to these two areas, I asked how a binge-type prenatal ethanol exposure might affect: (1) early postnatal development of striatal neurons …

Neural Mechanisms Of Language Development In Infancy, Scott Huberty, Christian O'Reilly, Virginia Carter Leno, Mandy Steiman, Sara J. Webb, Mayada Elsabbagh, The Basis Team

Publications

Understanding the neural processes underpinning individual differences in early language development is of increasing interest, as it is known to vary in typical development and to be quite heterogeneous in neurodevelopmental conditions. However, few studies to date have tested whether early brain measures are indicative of the developmental trajectory of language, as opposed to language outcomes at specific ages. We combined recordings from two longitudinal studies, including typically developing infants without a family history of autism, and infants with increased likelihood of developing autism (infant-siblings) (N = 191). Electroencephalograms (EEG) were recorded at 6 months, and behavioral assessments at …

Heterodyned Whole-Body Vibration Ameliorates Anxiety In Opioid-Use Disorder, Kailee Edwards, Braden Cunningham, Alfred Amendolara, Marryam Anwar, Jon Gonzales, Roshni Jogin, Wyatt Magoffin, Amar Paul, Ryan Perry, James Pike, Nathan Swallow, Steven Tung, Mary Seamons, Andrew Payne, John A. Kriak, David W. Sant, David W. Sant

Annual Research Symposium

No abstract provided.