Circadian Rhythmicity And Neurodevelopment Of Disco And Grim Mutations In Drosophila Melanogaster, 2019 University of Tennessee, Knoxville
Circadian Rhythmicity And Neurodevelopment Of Disco And Grim Mutations In Drosophila Melanogaster, John Patrick Story
EURēCA: Exhibition of Undergraduate Research and Creative Achievement
The death gene grim and its pathway for apoptosis has been studied extensively in Drosophila Melanogaster. The effects of grim mutations on circadian neurodevelopment and locomotor assays have yet to be investigated. Mutations in the gene disconnected (disco) has been shown to disrupt the normal development of the circadian circuitry, specifically the small ventro-lateral neurons (s-LNv’s). Which has shown to severely decrease rhythmicity during free-running periods. Alternatively, we have observed an increase in rhythmicity during free-running periods in grim mutations. Our goal is to investigate the neurodevelopment of the circadian circuitry and their associated locomotor activities in these Drosophila mutations.
Development Of An Intrahippocampal Kindling Model Of Epilepsy, 2019 Trinity College, Hartford Connecticut
Development Of An Intrahippocampal Kindling Model Of Epilepsy, Carter F. Jones
Senior Theses and Projects
Epilepsy is a neurological condition that affects about 1% of the global population. This debilitating condition is associated with overexcitation and ineffective inhibition of neuronal pathways in the brain causing serious and a diverse set of symptoms, most prominently seizures. While some antiepileptic drug (AED) regimes have been proven to be effective in treating this condition, there are many cases where the drugs do not do enough. The ketogenic diet (KD) has been used for decades as an effective anticonvulsant. Its powerful and natural processes result in some patients becoming seizure-free. Sometimes, these patients remain free of seizures even after …
The Role Of Ash1l During Human Neurodevelopment, 2019 University of South Carolina - Columbia
The Role Of Ash1l During Human Neurodevelopment, Anna Bagnell
Senior Theses
Autism spectrum disorders (ASD) are associated with defects in neuronal connectivity and are highly heritable. A significant proportion of ASD cases are of complex genetic etiology; complexity which might reflect the impact of gene-environment interactions. However, there is a gap in our understanding of the mechanisms that underlie the gene-environment interaction in autism complex etiology. Genome wide association studies in large ASD cohorts identified high risk variants associated with autism in genes that regulate histone modifications and remodel chromatin. These findings highlight the relevance of chromatin regulatory mechanisms in the pathology of ASD. Changes in Histone H3 methylation have been …
The Drosophila Neuroblasts: A Model System For Human Ribosomopathies, 2019 Louisiana State University and Agricultural and Mechanical College
The Drosophila Neuroblasts: A Model System For Human Ribosomopathies, Sonu Shrestha Baral
LSU Doctoral Dissertations
This dissertation describes the use of Drosophila neuroblasts (NBs) to model human ribosomopathies; the overall goal is to understand why specific stem cell and progenitor cell populations are the primary targets in nucleolar stress as seen in the ribosomopathies. Chapter 1 provides an overview of relevant literature. Chapter 2 describes nucleolar stress in Drosophila neuroblasts as a model for human ribosomopathies. For this, we induce nucleolar stress by using the UAS-GAL4 system to express RNAi that depletes Nopp140 transcripts, and we also employ homozygous, CRISPR-Cas9-generated Nopp140 gene disruptions with a systemic null phenotype (Nopp140-/-). Embryonic lethality was observed …
Role Of Withaferin A As A Neuroprotectant Against Beta Amyloid Induced Toxicity And Associated Mechanism, 2019 Florida International University
Role Of Withaferin A As A Neuroprotectant Against Beta Amyloid Induced Toxicity And Associated Mechanism, Sneham Tiwari
FIU Electronic Theses and Dissertations
Neurological disorders are the biggest concern globally and ageing contributes in worsening the disease scenarios. In AD or AD like diseases, there is abnormal accumulation of extracellular amyloid beta produced due to abnormal processing of the transmembrane amyloid precursor protein, by β and γ-secretases. It spreads in the cortical and limbic regions of the brain leading to neuronal toxicity, impairment in memory and neurological functions. Aβ deposition in the CNS is common in aging HIV patients. Neurotoxic protein Tat, results in increased Aβ in combination with drugs of abuse cocaine. We examined the role of Withaferin A, against Aβ induced …
Effects Of Chronic Ethanol Exposure On Stress Coping Style And Genetic States Of Zebrafish (Danio Rerio), 2019 University of Nebraska at Omaha
Effects Of Chronic Ethanol Exposure On Stress Coping Style And Genetic States Of Zebrafish (Danio Rerio), Alexander Goodman
UNO Student Research and Creative Activity Fair
Neurotransmitter systems are important in regulating the stress response. If a behavioral response is disproportional to a stressor it is characterized as anxiety-like behavior. Many anxiolytic compounds, such as ethanol, increase stressor engagement, but how these compounds interact with an organism on a neurogenetic level is less understood. In this study, I assessed the impact of chronic ethanol treatment on behavior and gene expression of GABAAreceptors subunits on two strains of zebrafish. Each strain was selectively bred to display the proactive or reactive stress coping style where proactive individuals will actively engage a stressor more than reactive individuals. …
Investigating Comt Influence On The Proactive-Reactive Stress Coping Axis In Zebrafish, 2019 University of Nebraska at Omaha
Investigating Comt Influence On The Proactive-Reactive Stress Coping Axis In Zebrafish, Sean T. Bresnahan, Ryan Y. Wong
UNO Student Research and Creative Activity Fair
Individuals of the same species often display differences in correlated suites of behaviors which are made conspicuous when challenges – stressful, fear-inducing, etc. – are presented. In many species, a specific suite of behaviors (risk-aversion, aggression, exploration, learning, and memory) characterize an alternative set of stress coping styles (proactive and reactive). Such behaviors are regulated in the brain by specific neurotransmitters along with proteins that regulate them. One neurotransmitter regulator protein, catechol-O-methyltransferase (COMT) shows higher baseline whole-brain expression in proactive relative to reactive animals. However, it is not known whether its expression is a cause or a consequence of the …
Ck2 Negatively Regulates 5-Ht4 Receptor Signaling In The Prefrontal Cortex And Mediates Depression-Like Behaviors, 2019 The Graduate Center, City University of New York
Ck2 Negatively Regulates 5-Ht4 Receptor Signaling In The Prefrontal Cortex And Mediates Depression-Like Behaviors, Julia Castello Saval
Dissertations, Theses, and Capstone Projects
The serotonergic system has been the major candidate in the pathophysiology of mood related disorders such as anxiety and major depressive disorder (MDD). Unfortunately, current antidepressant drugs are ineffective in 50% of the population and require chronic administration for a period of 3-6 weeks before the onset of therapeutic response. 5-HT4 receptor (5-HT4R) agonists have emerged as potential candidates for fast antidepressant action, since an antidepressant response can be achieved after 3 days of pharmacological administration in rodents.
This dissertation aims to investigate the role of casein kinase 2 (CK2) as a regulator of 5-HT4R expression …
The Master Synaptic Regulator: Activity Regulated Cytoskeleton Associated Protein, Arc, In Normal Aging And Diseases With Cognitive Impairment, 2019 The Graduate Center, City University of New York
The Master Synaptic Regulator: Activity Regulated Cytoskeleton Associated Protein, Arc, In Normal Aging And Diseases With Cognitive Impairment, Amber Khan
Dissertations, Theses, and Capstone Projects
Alzheimer’s disease (AD) is a progressive neurodegenerative disease with complex underlying pathogenic mechanisms. Epidemiological studies have forecasted that in the next 3 decades, the number of AD cases will rise to epidemic proportions with enormous medical, emotional and financial burdens impacting individuals affected and society. Among many risk factors for AD, advancing age is clearly essential and necessary. Revelation of molecular changes in synaptic activities leading to the prodromal, mild cognitive impairment (MCI) stage may help illuminate the course of pathogenic progression and its cause-effect relationship with various targets thereby enabling target-driven disease-modifying therapeutic agents for AD.
Activity-regulated cytoskeleton-associated (Arc) …
Post-Synaptic Mechanisms Of Early And Late Prepulse Inhibition In The Goldfish, 2019 The Graduate Center, City University of New York
Post-Synaptic Mechanisms Of Early And Late Prepulse Inhibition In The Goldfish, Daniel Bronson
Dissertations, Theses, and Capstone Projects
Sensorimotor gating, or prepulse inhibition (PPI), attenuates the startle response during sensory processing by limiting sensory input to the startle circuit. In the goldfish startle circuit, a single action potential in the Mauthner-cell (M-cell) triggers the startle response. PPI in the M-cell is mediated by multiple post-synaptic mechanisms, including the activation of a tonic, shunting inhibition as well as a voltage-sensitive conductance, both of which briefly reduce M-cell excitability. However, the specific channels and pathways that modulate PPI are not fully known. This work further characterizes the post-synaptic conductances that mediate PPI by blocking voltage-gated and inward-rectifying potassium channels, antagonizing …
The Integration Of Multiple Sources Of Sonic Hedgehog In The Spinal Cord Contribute To The Production Of First-Born Oligodendrocyte Precursor Cells Which Become Critical For Synapse Remodeling In Response To Adult Motor Neuron Injury, 2019 The Graduate Center, City University of New York
The Integration Of Multiple Sources Of Sonic Hedgehog In The Spinal Cord Contribute To The Production Of First-Born Oligodendrocyte Precursor Cells Which Become Critical For Synapse Remodeling In Response To Adult Motor Neuron Injury, Lev Starikov
Dissertations, Theses, and Capstone Projects
Oligodendrocyte precursor cells (OPCs) arise sequentially first from a ventral and then from a dorsal precursor domain during spinal cord development. Whether the sequential production of OPCs is of physiological significance has not been examined. Here I show that interrupting Sonic hedgehog (Shh) signaling originating from nascent ventricular zone derivatives (VZD), motor neurons and the lateral floor plate, almost completely blocks ventral but not dorsal oligodendrogenesis without noticeably affecting early tissue patterning and embryonic development. In the absence of ventral OPCs, dorsal OPCs increase proliferation and populate the entire spinal cord with increased density. In these mutant mice, dOPCs take …
Molecular Analysis Of Cone Photoreceptor Genesis From A Specific Retinal Progenitor Population, 2019 The Graduate Center, City University of New York
Molecular Analysis Of Cone Photoreceptor Genesis From A Specific Retinal Progenitor Population, Diego F. Buenaventura
Dissertations, Theses, and Capstone Projects
There are two types of photosensitive cells of the retina that contribute to image formation: Cone photoreceptors that mediate color discrimination and rods that provide photosensitivity in low-light conditions. Given the importance of cones in high acuity and color vision, deficiencies in this cell type that result from ailments such as retinitis pigmentosa and macular degeneration can lead to a debilitating loss of vision. Currently, one of the most pressing goals in the field of retinal development is the elucidation of the gene regulatory networks (GRN) involved in inducing an undifferentiated cell into becoming a functional cone photoreceptor.
Recently, an …
The Leucine-Rich Domain Of Rgnef: A Modifier Of Tdp-43 Toxicity In Drosophila Melanogaster., 2019 The University of Western Ontario
The Leucine-Rich Domain Of Rgnef: A Modifier Of Tdp-43 Toxicity In Drosophila Melanogaster., Benjamin Martin Withers
Electronic Thesis and Dissertation Repository
Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive degeneration of motor neurons. Rho Guanine Nucleotide Exchange factor (RGNEF) like other RNA-binding proteins, has been observed to form inclusions in the spinal cord motor neurons of both sporadic and familial cases of ALS. RGNEF has been determined to be a pro-survival factor under stress conditions. When comparing expression of different constructs of RGNEF in HEK293T cells, a Leucine-rich domain containing fragment of RGNEF (L-Rich) was found to form aggregates under metabolic stress that co-aggregated with TDP-43, another ALS-linked RNA-binding protein.
In this thesis, I used both …
The Role Of H3k4 Methyltransferases In Drosophila Memory, 2019 The University of Western Ontario
The Role Of H3k4 Methyltransferases In Drosophila Memory, Nicholas Raun
Electronic Thesis and Dissertation Repository
Gene transcription required for long-term memory requires the modification of histones. However, there are still many uncertainties about the identity and spatial expression of genes regulated by histone modifications during memory related processes. In this project I examined the role of Drosophila melanogaster methyltransferases Set1 and trx in courtship memory. Genetic knockdown of Set1 and trx in the mushroom body (MB) revealed that Set1 was necessary for short- and long-term memory, while trx was only required for long-term memory. Transcriptional profiling of MBs following trx-knockdown revealed expression changes in MB-enriched genes and genes involved in RNA processing. Among the …
Investigating The Role Of Tp53inp1 And Tp53inp2 In Neuronal Autophagy And Mitophagy, 2019 The University of Western Ontario
Investigating The Role Of Tp53inp1 And Tp53inp2 In Neuronal Autophagy And Mitophagy, Vidhyasree Shyam
Electronic Thesis and Dissertation Repository
Autophagy is highly conserved cellular process that functions in ensuring the turnover of proteins and organelles in a number of different cell types. Mitophagy is a selective form of autophagy which serves to target and rid the cell of damaged or superfluous mitochondria. The process is central to preventing the accumulation of defective mitochondria and is particularly important in neurons, which rely exclusively on mitochondria to sustain their immense metabolic needs. Dysregulation of autophagy is believed to contribute to the neurodegeneration seen in such disorders as Parkinson’s disease and cerebral ischemia. However, further understanding of the role of neuronal autophagy …
Absence Of Endothelial Α5Β1 Integrin Triggers Early Onset Of Experimental Autoimmune Encephalomyelitis Due To Reduced Vascular Remodeling And Compromised Vascular Integrity, 2019 The Scripps Research Institute
Absence Of Endothelial Α5Β1 Integrin Triggers Early Onset Of Experimental Autoimmune Encephalomyelitis Due To Reduced Vascular Remodeling And Compromised Vascular Integrity, Ravi Kant, Sebok K. Halder, Gregory J. Bix, Richard Milner
Sanders-Brown Center on Aging Faculty Publications
Early in the development of multiple sclerosis (MS) and its mouse model experimental autoimmune encephalomyelitis (EAE), vascular integrity is compromised. This is accompanied by a marked vascular remodeling response, though it is currently unclear whether this is an adaptive vascular repair mechanism or is part of the pathogenic process. In light of the well-described angiogenic role for the α5β1 integrin, the goal of this study was to evaluate how genetic deletion of endothelial α5 integrin (α5-EC-KO mice) impacts vascular remodeling and repair following vascular disruption during EAE pathogenesis, and how this subsequently influences clinical progression and inflammatory demyelination. Immunofluorescence staining …
Mechanisms Of Microglia Mediated Apolipoprotien E Neurotoxicity, 2019 CUNY City College
Mechanisms Of Microglia Mediated Apolipoprotien E Neurotoxicity, Pardeep Singh
Dissertations and Theses
No abstract provided.
The Effects Of A Ketone Body On Synaptic Transmission, 2019 University of Kentucky
The Effects Of A Ketone Body On Synaptic Transmission, Alexandra Elizabeth Stanback
Theses and Dissertations--Biology
The ketogenic diet is commonly used to control epilepsy, especially in cases when medications cannot. The diet typically consists of high fat, low carb, and adequate protein and produces a metabolite called acetoacetate. Seizure activity is characterized by glutamate excitotoxicity and therefore glutamate regulation is a point of research for control of these disorders. Acetoacetate is heavily implicated as the primary molecule responsible for decreasing glutamate in the synapse; it is believed that acetoacetate interferes with the transport of glutamate into the synaptic vesicles. The effects on synaptic transmission at glutamatergic synapses was studied in relation to the ketogenic diet …
Rapid No• Measures In Rat Nucleus Accumbens And Frontal Cortex Following Nasal Administration Of Nitroglycerin, 2019 University of Kentucky
Rapid No• Measures In Rat Nucleus Accumbens And Frontal Cortex Following Nasal Administration Of Nitroglycerin, Victoria A. Scott
Theses and Dissertations--Medical Sciences
Nitric Oxide (NO) is a powerful endogenous free radical that has numerous biological functions including vasodilation and serves as a post synaptic second messenger in the central nervous system (CNS). Numerous studies implicate NO• involvement in CNS disorders such as schizophrenia and drug abuse. These studies address the direct in vivo determination of an FDA-approved NO• donor (nitroglycerin) on extracellular levels of NO• in the frontal cortex and core of the nucleus accumbens in a lightly anesthetized rat. State-of-the-art in vivo amperometric recording techniques coupled with a novel 4-channel low noise pre-amplifier system and new generation microelectrode arrays (MEAs) will …
Molecular Basis Of Membrane Pore Formation By Amyloid Beta Peptide, 2019 University of Central Florida
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 …