Neuroscience and Neurobiology Commons^™

Effect Of Propionic Acid-Derivative Ibuprofen On Neural Stem Call Differentiation; A Potential Link To Autism Spectrum Disorder, Aseelia Samsam

Honors Undergraduate Theses

Propionic acid (PPA) is a short chain fatty acid that is produced by the human gut microbiome. Propionate, butyrate and acetates are the end products of the fermentation of the complex carbohydrates by human gut friendly microbiome and are being used as sources of energy in our body. PPA is used as a food preservative against molds in various daily products and has been implicated in the pathogenesis of autism. In a recent study we showed that PPA in human neuronal stem cell (NSC) culture increases the astrocyte population and decreases the neuronal number and increases the inflammatory cytokines. In …

Investigating The Role Of Neuronal Aging In Fragile X-Associated Tremor/Ataxia Syndrome, Katlin Marie Hencak

Honors Undergraduate Theses

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an X-linked late-onset neurodegenerative disorder caused by a noncoding trinucleotide repeat expansion in the FMR1 gene. This gene produces fragile x mental retardation protein (FMRP), an RNA binding protein whose targets are involved in brain development and synaptic plasticity. One of the proposed mechanisms of FXTAS pathogenesis is an RNA gain-of-function in which the repeat expansion causes toxic mRNA that sequesters important proteins in the cell, interfering with their functions. Another suggested method of pathogenesis is through a mutant protein called FMRpolyG. This protein results from repeat-associated non-AUG (RAN) translation, in which the expanded …

Molecular Basis Of Membrane Pore Formation By Amyloid Beta Peptide, Nabin Kandel

Electronic Theses and Dissertations

Alzheimer's Disease (AD) is a neurodegenerative disorder that affects around 50 million people worldwide and causes cognitive decline, brain atrophy and death. Despite extensive basic and clinical studies and drug development efforts, currently no effective treatments are available for AD. The amyloid β (Aβ) peptide is neurotoxic and is tightly associated with AD pathology, but the molecular mechanism of its action remains unclear. There are various forms of Aβ in the brain, ranging from the full length Aβ1-42 to shorter peptides, such as a strongly toxic Aβ25-35 fragment. The Amyloid Cascade Hypothesis (ACH) postulated that extracellular Aβ deposits cause the …

Targeted Delivery Of A Therapeutic Protein For The Treatment Of Alzheimer's Disease, Heather Holman

Honors Undergraduate Theses

Neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease are linked to mitochondrial dysfunction and the underexpression of TOM40, a protein with chaperone-like qualities that is responsible for transporting precursor proteins into the mitochondria. Overexpression of TOM40 is reported to partially restore mitochondrial dysfunction and decrease the accumulation of neurotoxic aggregates of α-synuclein. Our goal is to develop an effective method for delivery of TOM40 protein to the brain.

Previous studies have used lentiviruses to carry TOM40 into the hippocampus of α-synuclein transgenic mice. The disadvantage of lentiviral transfection is the random insertions of the target gene into the host …

Simultaneous Use Of Physiological Sensors For A Neuromarketing Task, Charles Descheneaux

Electronic Theses and Dissertations

Physiological measurements have become more popular in Psychological research over the past ten years. These advancements allowed different objective sensors to become another measurement tool in a scientific arsenal of collecting data. Traditionally, performance and after task subjective measures have been used for most studies in Psychological research. With the opportunity to use these subjective measures along with objective measures, more data can be collected during research and therefore potentially produce better quality conclusions. Eye Tracking (ET), functional near infrared (fNIR), transcranial Doppler ultrasound (TCD), electrocardiogram (EKG) and the electroencephalogram (EEG) have shown great promise in their ability to produce …

Investigating The Role Of The Caspase-6 Cleavage Fragment Of Mutant Huntingtin In Huntington Disease Pathogenesis, Jourdan A. Mckinnis

Honors Undergraduate Theses

Huntington disease (HD) is a devastating and fatal neurodegenerative disease. At the moment, no disease modifying therapies are available, with only symptomatic treatment offered to alleviate psychiatric and some types of motor deficits. As a result, many people will continue to suffer and die from this disease. Small molecule therapies have failed to provide benefit in HD, necessitating more complex gene therapy approaches and the identification of less traditional therapeutic targets. A previous study demonstrated that preventing cleavage of the huntingtin (HTT) protein, the protein that when mutated causes HD, by caspase 6 (C6) at amino acid 586 prevents the …

Alpha-Synuclein: Insight Into The Hallmark Of Parkinson's Disease As A Target For Quantitative Molecular Diagnostics And Therapeutics, Baggio A. Evangelista

Honors Undergraduate Theses

Parkinson’s disease (PD) is the second-most common neurodegenerative disease after Alzheimer’s disease. With 500,000 individuals currently living with Parkinson’s and nearly 60,000 new cases diagnosed each year, this disease causes significant financial burden on the healthcare system - amassing to annual expenditures totaling 200 billion dollars; predicted to increase through 2050. The disease phenotype is characterized by a combination of a resting tremor, bradykinesia, muscular rigidity, and depression due to dopaminergic neuronal death in the midbrain. The cause of the neurotoxicity has been largely discussed, with strong evidence suggesting that the protein, alpha-Synuclein, is a key factor. Under native conditions, …

The Relationship Between Sleep, Working Memory, And Decision Making In Young And Old Adult Populations, Melissa G. Merz

Honors Undergraduate Theses

Sleep is known to influence basic tasks concerning working memory, reaction time and executive functioning (Silva, Wang, Ronda, Wyatt, & Duffy, 2010; Nebes, Buysse, Halligan, Houck, & Monk, 2009). However, the amount that sleep influences these functions varies from study to study possibly due to differences in age and task design. Aim 1A of this study is to determine if sleep quality affects working memory. Aim 1B of this study is to determine if age affects sleep quality and working memory in comparison of young and old adult populations. Finally, Aim 2 of this study is to determine if there …

Evaluating Competition Between Verbal And Implicit Systems With Functional Near-Infrared Spectroscopy, Troy A. Schiebel

Honors Undergraduate Theses

In category learning, explicit processes function through the prefrontal cortex (PFC) and implicit processes function through the basal ganglia. Research suggested that these two systems compete with each other. The goal of this study was to shed light on this theory. 15 undergraduate subjects took part in an event-related experiment that required them to categorize computer-generated line-stimuli, which varied in length and/or angle depending on condition. Subjects participated in an explicit "rule-based" (RB) condition and an implicit "information-integration" (II) condition while connected to a functional near-infrared spectroscopy (fNIRS) apparatus, which measured the hemodynamic response (HR) in their PFC. Each condition …

The Effect Of Caffeine On Migraine Headaches, Deborah Shimshoni

Honors Undergraduate Theses

As the most widely consumed drug around the globe, there is a vast array of contradicting research available on caffeine. One of the most debated and researched topics on caffeine is its effect on the brain. Meanwhile, the data on the neurological condition of migraine has information scattered throughout countless research articles and experiments.

Although neither migraine or caffeine are completely understood by the medical world, this analysis attempts to give a more coherent understanding of the relationship between the two. This is done by first understanding the known and theorized mechanisms of caffeine as well as the pathologies of …

Vitamin D Clinical Relevance In The Recovery From Traumatic Brain Injury Among The Military Population, Yuisa M. Colón

Honors Undergraduate Theses

Background: Traumatic brain injury (TBI) still remains a difficult disorder to treat. TBI has been associated to chronic neuroinflammation and a high risk for neurodegenerative disorders. Since 2001 between ten to twenty percent of all deployed military members have suffered a combat-related TBI. Nearly twenty to thirty percent of those will experience chronic cognitive, behavioral and somatic symptoms after suffering a TBI.
Methods: The objective of this review is to evaluate current literature examining vitamin D as a neurosteroid with protective properties and its clinical relevance after traumatic brain injury. Vitamin D is known to participate in neurobiological …

Amyotrophic Lateral Sclerosis: Mechanism Behind Mutant Sod Toxicity And Improving Current Therapeutic Strategies, Cassandra Dennys

Electronic Theses and Dissertations

Amyotrophic Lateral Sclerosis (ALS) is an always lethal motor neuron disease with unknown pathogenesis. Inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) have limited neuroprotection in some models of motor neuron degeneration. However the direct effect of Hsp90 inhibition on motor neurons is unknown. Here we show that Hsp90 inhibition induced motor neuron death through activation of the P2X7 receptor. Motor neuron death required phosphatase and tensein homolog (PTEN)-mediated inhibition of the PI3K/AKT pathway leading to Fas receptor activation and caspase dependent death. The relevance of Hsp90 for motor neuron survival was investigated in mutant Cu/Zn superoxide dismutase …

Mcp-1 And App Involvement Of Glial Differentiation And Migration Of Neuroprogenitor Cells, Emmanuel Vrotsos

Electronic Theses and Dissertations

Neuroprogenitor cells are an important resource because of their potential to replace damaged cells in the brain caused by trauma and disease. It is of great importance to better understand which factors influence the differentiation and migration of these cells. Previously it has been reported that neuroprogenitor cells undergoing apoptotic stress have increased levels of Amyloid precursor protein (APP) and increased APP expression results in glial differentiation. APP activity was also shown to be required for staurosporine induced glial differentiation of neuroprogenitor cells. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that is expressed during inflammatory. The binding of MCP-1 to …

The Endocytic Protein Numb Regulates App Metabolism And Notch Signaling: Implications For Alzheimer's Disease, George Kyriazis

Electronic Theses and Dissertations

Increased production of amyloid beta (A-beta) peptide, via altered proteolytic cleavage of amyloid protein precursor (APP), and abnormalities in neuronal calcium homeostasis play central roles in the pathogenesis of Alzheimer's disease (AD). Notch1, a membrane receptor that controls cell fate decisions during development of the nervous system, has been linked to AD because it is a substrate for the gamma-secretase protein complex in which mutations cause early-onset inherited AD. Numb is an evolutionarily conserved endocytic adapter involved in the internalization of transmembrane receptors. Mammals produce four Numb isoforms that differ in two functional domains, a phosphotyrosine-binding domain (PTB) and a …

Glutamate Excitotoxicity In Epilepsy And Ischemia, Mangala Meenakshi Soundarapandian

Electronic Theses and Dissertations

'Excitotoxicity' represents the excitatory amino acid mediated degeneration of neurons. Glutamate is the major excitatory neurotransmitter in the brain. Glutamate excitotoxicity has been implicated in a number of neurodegenerative disorders like Stroke, Epilepsy, Alzheimer's disease and traumatic brain injury. This neurotoxicity is summed up by the 'glutamate hypothesis' which describes the cause of neuronal cell death as an excessive release of glutamate causing over excitation of the glutamate receptors and subsequent increase in influx of calcium leading to cell death. An effort to counteract this neurotoxicity has lead to the development of glutamate receptor antagonists that can effectively serve as …