Medical Neurobiology Commons^™

Investigation Of The Role Of Heparin-Binding Pocket In Amyloid Fibrils Formation Of Fgf-1, I Gusti Ayu Agung Septiari

Graduate Theses and Dissertations

Human acidic fibroblast growth factor (aFGF/hFGF-1) is one of the promising molecules to be investigated to generate an in-depth understanding of the pathological mechanism of Alzheimer's disease (AD) neurodegenerative disorder characterized by the presence of amyloid fibrils. Some in vivo and human brain tissue studies proved the correlation of high-level expression of FGF-1-induced neuroinflammation and the occurrence of AD. The presence of amyloid fibrils as a hallmark of AD can be related to the generic property of the proteins to form amyloid fibrils; High level of FGF-1, in this case, may contribute to the formation of amyloid fibrils. As a …

Targeting The Transferrin Receptor To Develop Erythropoietin For Alzheimer’S Disease, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

"Alzheimer’s disease (AD) is the sixth leading cause of death in the United States with approximately 5.8 million Americans currently living with AD. Due to the lack of a disease modifying treatment for AD and the aging baby boomer generation, this number is projected to grow to 13.8 million by 2050 (Gaugler et al., 2019). Amyloid-beta (Aβ) plaque accumulation, one of the major pathological hallmarks of AD, can begin > 20 years before clinical symptoms of AD. By the time AD is clinically diagnosed, neuronal loss and neuropathological lesions (Aβ plaques and tau tangles) have already occurred in many brain regions …

Two Nights Of Recovery Sleep Restores Hippocampal Connectivity But Not Episodic Memory After Total Sleep Deprivation, Ya Chai, Zhuo Fang, Fan Nils Yang, Sihua Xu, Yao Deng, Andrew Raine, Jieqiong Wang, Meichen Yu, Mathias Basner, Namni Goel, Junghoon J. Kim, David A. Wolk, John A. Detre, David F. Dinges, Hengyi Rao

Publications and Research

Sleep deprivation significantly impairs a range of cognitive and brain function, particularly episodic memory and the underlying hippocampal function. However, it remains controversial whether one or two nights of recovery sleep following sleep deprivation fully restores brain and cognitive function. In this study, we used functional magnetic resonance imaging (fMRI) and examined the effects of two consecutive nights (20-hour time-in-bed) of recovery sleep on resting-state hippocampal connectivity and episodic memory deficits following one night of total sleep deprivation (TSD) in 39 healthy adults in a controlled in-laboratory protocol. TSD significantly reduced memory performance in a scene recognition task, impaired hippocampal …

Clinical And Basic Research Investigations Into The Long‐Term Effects Of Prenatal Opioid Exposure On Brain Development, Taylor Boggess, W. Chris Risher

Biomedical Sciences

Coincident with the opioid epidemic in the United States has been a dramatic increase in the number of children born with neonatal abstinence syndrome (NAS), a form of withdrawal resulting from opioid exposure during pregnancy. Many research efforts on NAS have focused on short‐term care, including acute symptom treatment and weaning of the infants off their drug dependency prior to authorizing their release. However, investigations into the long‐term effects of prenatal opioid exposure (POE) on brain development, from the cellular to the behavioral level, have not been as frequent. Given the importance of the perinatal period for human brain development, …

Determining The Genetic Control Of Neural Tube Malformation Through Genetic Interactions With Idgf3, Elli N. Fox

Honors Projects

Genetic mutations disrupting human neural tube formation can lead to birth defects such as spina bifida and anencephaly. Defects can result in lack of neural tube closure in either the caudal (spina bifida) or cranial (anencephaly) regions. Little is known about the genes that cause these malformations. Researchers have been using the model organism Drosophila melanogaster in an attempt to determine genes responsible for neural tube malformations. Recently, an ortholog of human chitin-like protein, imaginal disc growth factor 3 (Idgf3), has been identified as important in the proper formation of Drosophila egg dorsal appendages. However, the molecular mechanism responsible for …

Regulating Neuronal Growth With Structurally Defined Glycans, Gabriella D. Hartman

Honors Theses

Chondroitin sulfate proteoglycans (CSPGs) and keratan sulfate proteoglycans (KSPGs) play an important role in neural development. Aggrecan, a CSPG, operates in the neural extracellular matrix where it negatively regulates neurite outgrowth to prevent aberrant process formation. Unfortunately, this aggrecan or CSPG-rich/KSPG-rich barrier can also prevent neuronal regeneration, which contributes to the inability to repair brain and spinal cord injuries. Removal of CSPGs and KSPGs has been shown to increase neurite outgrowth. We extend these findings by testing the ability of structurally-defined glycans to outcompete aggrecan and allow neurite outgrowth. Our overall goal is to determine if there is a particular …

The Current Neuroscientific Understanding Of Alzheimer's Disease, Rachel A. Brandes

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Alzheimer’s disease is a degenerative neurological illness characterized by the deterioration of brain regions implicated in memory and cognitive function. While researchers have yet to find a cure or effective treatment, they have gained a better understanding of its pathology and development. Through years of neuroscience research, scientists have discovered much of what happens in the brain during Alzheimer’s disease onset and how this causes its symptoms; many hypotheses regarding this aspect of the illness involve temporal lobe atrophy, neurofibrillary tangles, and amyloid plaques. Although Alzheimer’s disease affects millions of people every day, it seems that most are unaware of …

Depressed Neuromuscular Transmission Causes Weakness In Mice Lacking Bk Potassium Channels, Xueyong Wang, Steven R.A. Burke, Robert J. Talmadge, Andrew A. Voss, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Mice lacking functional large-conductance voltage- and Ca2+-activated K+ channels (BK channels) are viable but have motor deficits including ataxia and weakness. The cause of weakness is unknown. In this study, we discovered, in vivo, that skeletal muscle in mice lacking BK channels (BK−/−) was weak in response to nerve stimulation but not to direct muscle stimulation, suggesting a failure of neuromuscular transmission. Voltage-clamp studies of the BK−/− neuromuscular junction (NMJ) revealed a reduction in evoked endplate current amplitude and the frequency of spontaneous vesicle release compared with WT littermates. Responses to 50-Hz stimulation indicated a reduced probability of vesicle release …

Synaptic Protein Expression In Human Postmortem Brain Tissue Of Autism Spectrum Disorder, Alexandra Duggan

Undergraduate Honors Theses

It is estimated that one in 59 children in the US are affected by autism spectrum disorder (ASD). ASD is distinguished by social and communication deficits that can be displayed throughout a wide range of severity. This resulting spectrum of behaviors observed in ASD suggests that a complex etiology is involved. Previous studies have shown a genetic susceptibility to autism including paternal age, twin and sibling concordance. Genetic sequencing of those affected as well as first order relatives have identified alterations in genes associated with neuronal synaptic communication. However, very little information is available regarding the pathophysiology of synapses in …

Acute Disseminated Encephalomyelitis, Ashan Hatharasinghe, Hossein Akhondi, Don Pepito

HCA Healthcare Journal of Medicine

Introduction: Acute Disseminated Encephalomyelitis (ADEM) is a rare autoimmune demyelinating disorder of the central nervous system. Clinical manifestations include encephalopathy, motor deficits, ataxia, and meningeal signs. In most cases, ADEM is preceded by either vaccination or viral illness. Here, we present a case with neither of the two predisposing elements.

Discussion: A 28-year-old Hispanic female presenting with substance use and suicidal ideation was placed on an involuntary psychiatric hold, started on olanzapine and scheduled for a psychiatric facility transfer. The following day, she was noted to have neurological deficits when ambulating. Computed tomography of the brain showed a right frontal …

Adverse Aftereffects Of Methotrexate As Chemotherapy On Cognitive Deficits In Rat Models, Jubin Kang

Senior Honors Theses

Patients with acute lymphoblastic leukemia have a high five-year survival rate thanks to methotrexate (MTX). However, cognitive side effects are reported, characterized as chemo brain. The study investigated if impulsiveness is part of the aberrant cognitive functions after being exposed to MTX in the early stage of physical development. Adolescent rats were injected with either phosphate-buffered saline (PBS) or MTX. The novel object recognition (NOR) task was conducted a month after the injections to measure the memory deficits. The discounting task was performed after the rats completed training on a fixed-ratio one schedule for both levers. The NOR test showed …

Anxiety In Alzheimer's Disease, Zachary Cooper

Senior Honors Theses

Researchers familiar with Alzheimer’s disease have often noted the presence of comorbid anxiety symptomatology. Likewise, the occurrence of anxiety before the development of Alzheimer’s disease has been prevalent enough to warrant attention. This review seeks to elaborate on the pathophysiology behind these two conditions, and to accentuate overlapping aspects that promote a causal relationship between these two pathologies on the macroscopic and cellular levels. Subsequent evidence will show that these pathologies are not independent of each other, and that cellular mechanisms of pathology hint at their interrelatedness. Areas requiring further research that would clarify the relationship between Clinical Anxiety and …

Covid 19 What You Need To Know, Dawn P. Wooley, Giancarlo Mariani, Craig Woolley, Laura M. Luehrmann

Neuroscience, Cell Biology & Physiology Faculty Publications

This is the first presentation in the new Shelter-in-Place lecture series. This first lecture is two-fold. First, it covers the basics of the COVID-19 virus including: how it spreads, possible origin, and other pertinent information. This portion of the presentation was followed by an overview of the international recruitment efforts in response to the virus, including: student perspectives, recruitment methods, and other important information.

Assay Development For Isolation And Characterization Of Anticancer Properties Of Marine Fungi, Kyra Ricci

Honors Theses

Metabolites from fungi have potential use in the drug discovery process and have been used in the past to develop therapeutic agents for human use. Initial characterization of potential therapeutic properties of fungi is thus an important first step in identifying novel therapeutic compounds. In the present study, marine fungi were isolated from Myrtle Beach and assayed for anticancer properties using the soft agar colony formation assay in a 3D in vitro cellular environment. Many species were isolated from environmental samples, displaying unique morphologies and growth patterns. To optimize the soft agar assay in a six-well cell culture plate for …

Time For A Change? Brain Activity And Behavioral Performance Reveal Different Dynamics At Short, Intermediate, And Long Delay Intervals During A Delay Discounting Task, Conrad A. Mohr-Eymer

Honors Thesis

In our day to day lives, the ability to make goal-oriented decisions plays a crucial role in both our work and social lives. Therefore, researchers have examined how factors such as a varying reward or delay may affect decision making. One’s performance when making intertemporal choices, decisions made between a smaller and sooner (SS) reward and a larger and later (LL) reward, are often examined to study these factors. Although time and reward magnitude are important dimensions when individuals make decisions during delay discounting, little is known about the relationship between time perception, reward magnitude, and underlying neural mechanisms. To …

Evidence That Brain-Reactive Autoantibodies Contribute To Chronic Neuronal Internalization Of Exogenous Amyloid-Β1-42 And Key Cell Surface Proteins During Alzheimer's Disease Pathogenesis, Eric L Goldwaser, Nimish K Acharya, Hao Wu, George A Godsey, Abhirup Sarkar, Cassandra A Demarshall, Mary C Kosciuk, Robert G Nagele

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Blood-brain barrier (BBB) permeability is a recognized early feature of Alzheimer's disease (AD). In the present study, we examined consequences of increased BBB permeability on the development of AD-related pathology by tracking selected leaked plasma components and their interactions with neurons in vivo and in vitro. Histological sections of cortical regions of postmortem AD brains were immunostained to determine the distribution of amyloid-β1-42 (Aβ42), cathepsin D, IgG, GluR2/3, and alpha7 nicotinic acetylcholine receptor (α7nAChR). Results revealed that chronic IgG binding to pyramidal neurons coincided with internalization of Aβ42, IgG, GluR2/3, and α7nAChR as well as lysosomal compartment expansion in these …

Pyrosequencing Analysis Of Irs1 Methylation Levels In Schizophrenia With Tardive Dyskinesia, Yanli Li, Kesheng Wang, Ping Zhang, Junchao Huang, Ying Liu, Zhiren Wang, Yongke Lu, Shuping Tan, Fude Yang, Yunlong Tan

Pharmacology, Physiology and Toxicology

Tardive dyskinesia (TD) is a serious side effect of certain antipsychotic medications that are used to treat schizophrenia (SCZ) and other mental illnesses. The methylation status of the insulin receptor substrate 1 (IRS1) gene is reportedly associated with SCZ; however, no study, to the best of the authors' knowledge, has focused on the quantitative DNA methylation levels of the IRS1 gene using pyrosequencing in SCZ with or without TD. The present study aimed to quantify DNA methylation levels of 4 CpG sites in the IRS1 gene using a Chinese sample including SCZ patients with TD and without TD (NTD) and …

Regulation Of Synaptic Development By Astrocyte Signaling Factors And Their Emerging Roles In Substance Abuse, Christopher D. Walker, W. Chris Risher, Mary-Louise Risher

Biomedical Sciences

Astrocytes have critical functions throughout the central nervous system (CNS) and have emerged as regulators of synaptic development and function. With their highly complex morphologies, they are able to interact with thousands of synapses via peripheral astrocytic processes (PAPs), ensheathing neuronal axons and dendrites to form the tripartite synapse. In this way, astrocytes engage in crosstalk with neurons to mediate a variety of CNS processes including the regulation of extracellular matrix protein signaling, formation and maintenance of the blood-brain barrier (BBB), axon growth and guidance, homeostasis of the synaptic microenvironment, synaptogenesis, and the promotion of synaptic diversity. In this review, …

Brain Damage Associated With Impaired Sentence Processing In Acute Aphasia, Sigfus Kristinsson, Helga Thors, Grigori Yourganov, Sigridur Magnusdottir, Haukur Hjaltason, Brielle C. Stark, Alexandra Basilakos, Dirk B. Den Ouden, Leo Bonilha, Chris Rorden, Gregory Hickok, Argye E. Hillis, Julius Fridriksson

Communication Sciences and Disorders Faculty Articles and Research

Left-hemisphere brain damage commonly affects patients' abilities to produce and comprehend syntactic structures, a condition typically referred to as “agrammatism.” The neural correlates of agrammatism remain disputed in the literature, and distributed areas have been implicated as important predictors of performance, for example, Broca's area, anterior temporal areas, and temporo-parietal areas. We examined the association between damage to specific language-related ROIs and impaired syntactic processing in acute aphasia. We hypothesized that damage to the posterior middle temporal gyrus, and not Broca's area, would predict syntactic processing abilities. One hundred four individuals with acute aphasia (< 20 days poststroke) were included in the study. Structural MRI scans were obtained, and all participants completed a 45-item sentence–picture matching task. We performed an ROI-based stepwise regression analyses to examine the relation between cortical brain damage and impaired comprehension of canonical and noncanonical sentences. Damage to the posterior middle temporal gyrus was the strongest predictor for overall task performance and performance on noncanonical sentences. Damage to the angular gyrus was the strongest predictor for performance on canonical sentences, and damage to the posterior superior temporal gyrus predicted noncanonical scores when performance on canonical sentences was included as a cofactor. Overall, our models showed that damage to temporo-parietal and posterior temporal areas was associated with impaired syntactic comprehension. Our results indicate that the temporo-parietal area is crucially implicated in complex syntactic processing, whereas the role of Broca's area may be complementary.

A Phantom Of The Past: Withdrawal From Meprobamate Presenting With Focal Seizures., Thomas M. Zink, John E. Erickson

Journal of Maine Medical Center

Introduction: Meprobamate (Miltown, Equinil) is a sedative-hypnotic medication that first gained popularity as an anxiolytic and later as a muscle relaxant. It is a major metabolite of the more commonly used muscle relaxant carisoprodol (Soma). In vitro and electroencephalogram studies demonstrated that meprobamate modulates gama-aminobutyric acid (GABA) receptors, similar to barbiturates. Withdrawal from meprobamate manifests in symptoms ranging from mild anxiety to severe autonomic instability and death. Meprobamate is rarely prescribed, but is still given to a small subset of elderly patients.

Clinical findings: In this case of meprobamate withdrawal, the patient initially displayed altered mental status and recurrent seizures …