Molecular and Cellular Neuroscience Commons^™

Regulation Of The Amyloid Precursor Protein By Prostaglandin J2, A Mediator Of Inflammation: Relevance To Alzheimer’S Disease, Teneka L. Jean-Louis

All Graduate Works by Year: Dissertations, Theses, and Capstone Projects

Inflammation plays a major role in Alzheimer’s disease (AD). Investigating how specific mediators of inflammation contribute to neurodegeneration in AD is crucial. Our studies focused on cyclooxygenases, which are key enzymes in inflammation and highly relevant to AD. Cyclooxygenases (COX -1, constitutive; COX-2, inducible) have emerged as important determinants of AD pathogenesis and progression. COX-2 is highly induced in AD, correlating with AD severity, and COX-1 is also involved in AD. Cyclooxygenases are the rate-limiting enzymes that convert arachidonic acid into prostaglandins (PGs), the principal mediators of CNS neuroinflammation.

The overall GOAL of these studies was to address the ...

C. Elegans Avoids Toxin-Producing Streptomyces Using A Seven Transmembrane Domain Chemosensory Receptor, Alan Tran, Angelina Tang, Colleen O’Loughlin, Anthony Balistreri, Eric Chang, Doris Coto Villa, Joy Li, Aruna Varshney, Vanessa Jimenez, Jacqueline Pyle, Bryan Tsujimoto, Christopher Wellbrook, Christopher Vargas, Alex Duong, Nebat Ali, Sarah Matthews, Samantha Levinson, Sarah Woldemariam, Sami Khuri, Martina Bremer, Daryl Eggers, Noelle L’Etoile, Laura Miller Conrad, Miri Vanhoven

Faculty Publications, Chemistry

Predators and prey co-evolve, each maximizing their own fitness, but the effects of predator–prey interactions on cellular and molecular machinery are poorly understood. Here, we study this process using the predator Caenorhabditis elegans and the bacterial prey Streptomyces, which have evolved a powerful defense: the production of nematicides. We demonstrate that upon exposure to Streptomyces at their head or tail, nematodes display an escape response that is mediated by bacterially produced cues. Avoidance requires a predicted G-protein-coupled receptor, SRB-6, which is expressed in five types of amphid and phasmid chemosensory neurons. We establish that species of Streptomyces secrete dodecanoic ...

C. Elegans Avoids Toxin-Producing Streptomyces Using A Seven Transmembrane Domain Chemosensory Receptor, Alan Tran, Angelina Tang, Colleen T. O’Loughlin, Anthony Balistreri, Eric Chang, Doris Coto Villa, Joy Li, Aruna Varshney, Vanessa Jimenez, Jacqueline Pyle, Bryan Tsujimoto, Christopher Wellbrook, Christopher Vargas, Alex Duong, Nebat Ali, Sarah Y. Matthews, Samantha Levinson, Sarah Woldemariam, Sami Khuri, Martina Bremer, Daryl K. Eggers, Noelle L’Etoile, Laura C. Miller Conrad, Miri Vanhoven

Daryl K. Eggers

Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, Aniruddho Chokroborty-Hoque

Electronic Thesis and Dissertation Repository

Maternal alcohol consumption during pregnancy results in a spectrum of behavioural and cognitive deficits collectively known as Fetal Alcohol Spectrum Disorders (FASD). Currently, little is know about if and how the external environment may modulate these deficits. I have used C57BL/6 mice to study this interaction between prenatal alcohol exposure and the postnatal environment. Alcohol exposure during synaptogenesis produces high levels of anxiety-like traits and decreased memory performance. Alcohol-exposed mice (and matched unexposed controls) were put in 'environmentally-enriched' conditions of voluntary exercise, physical activities and cognitive stimulation to ascertain the effects of a positive postnatal environment. The results show ...

Elucidating Mechanisms Of Protein Aggregation In Alzheimer’S Disease Using Antibody-Based Strategies., Benjamin A. Colvin

Dissertations

Alzheimer’s Disease (AD) is a devastating neurodegenerative disorder. There are two characteristic histopathological hallmarks in the brain: senile plaques and neurofibrillary tangles, composed of insoluble aggregates of the amyloids Amyloid-β (Aβ) and tau protein, respectively. These diagnostic markers, though distinctive, are not apparent effectors of AD pathology. Evidence has mounted suggesting smaller soluble aggregates (oligomers) of Aβ or tau are the true drivers of disease progression. This dissertation presents several amyloid biophysics projects. Aggregate biophysical parameters such as weight, shape, and conformation were measured using a range of methodologies, including Multiangle Light Scattering, Dynamic Light Scattering, UV-Circular Dichroism, UV-Fluorescence ...

Dynamic Control Of Dendritic Mrna Expression By Cnot7 Regulates Synaptic Efficacy And Higher Cognitive Function, Rhonda L. Mcfleder, Fernanda Mansur, Joel D. Richter

GSBS Student Publications

Translation of mRNAs in dendrites mediates synaptic plasticity, the probable cellular basis of learning and memory. Coordination of translational inhibitory and stimulatory mechanisms, as well as dendritic transport of mRNA, is necessary to ensure proper control of this local translation. Here, we find that the deadenylase CNOT7 dynamically regulates dendritic mRNA translation and transport, as well as synaptic plasticity and higher cognitive function. In cultured hippocampal neurons, synaptic stimulation induces a rapid decrease in CNOT7, which, in the short-term, results in poly(A) tail lengthening of target mRNAs. However, at later times following stimulation, decreased poly(A) and dendritic localization ...

Neuroanatomical Tracing Of The Gut -- Brain Axis, Ricardo P. Torres, Elizabeth A. Davis, Coltan G. Parker, Megan J. Dailey

Phenotypic Plasticity Research Experience for Community College Students

This poster summarizes a variety of methods to further characterize the gut-brain axis by tracing motor and sensory nerves between the gut and brain and identifying cell bodies in the sensory ganglia. Determines the meth method to trace the sensory and motor nerves was through fluorescence and the best method to identify sensory neuron cell bodies was the Nissi stain.

The Circadian Clock Gene Bmal1 Coordinates Intestinal Regeneration, Kyle Stokes, Abrial Cooke, Hanna Chang, David R. Weaver, David T. Breault, Phillip Karpowicz

Neurobiology Publications and Presentations

BACKGROUND and AIMS: The gastrointestinal syndrome is an illness of the intestine caused by high levels of radiation. It is characterized by extensive loss of epithelial tissue integrity, which initiates a regenerative response by intestinal stem and precursor cells. The intestine has 24-hour rhythms in many physiological functions that are believed to be outputs of the circadian clock: a molecular system that produces 24-hour rhythms in transcription/translation. Certain gastrointestinal illnesses are worsened when the circadian rhythms are disrupted, but the role of the circadian clock in gastrointestinal regeneration has not been studied.

METHODS: We tested the timing of regeneration ...

A Mathematical Model For Selective Differentiation Of Neural Progenitor Cells On Micropatterned Polymer Substrates, Cory L. Howk, Howard A. Levine, Michael W. Smiley, Surya K. Mallapragada, Marit Nilsen-Hamilton, Jisun Oh, Donald S. Sakaguchi

Surya K Mallapragada

The biological hypothesis that the astrocyte-secreted cytokine, interleukin-6 (IL6), stimulates differentiation of adult rat hippocampal progenitor cells (AHPCs) is considered from a mathematical perspective. The proposed mathematical model includes two different mechanisms for stimulation and is based on mass–action kinetics. Both biological mechanisms involve sequential binding, with one pathway solely utilizing surface receptors while the other pathway also involves soluble receptors. Choosing biologically-reasonable values for parameters, simulations of the mathematical model show good agreement with experimental results. A global sensitivity analysis is also conducted to determine both the most influential and non-influential parameters on cellular differentiation, providing additional insights ...

A Mathematical Model For Selective Differentiation Of Neural Progenitor Cells On Micropatterned Polymer Substrates, Cory L. Howk, Howard A. Levine, Michael W. Smiley, Surya K. Mallapragada, Marit Nilsen-Hamilton, Jisun Oh, Donald S. Sakaguchi

Marit Nilsen-Hamilton

The biological hypothesis that the astrocyte-secreted cytokine, interleukin-6 (IL6), stimulates differentiation of adult rat hippocampal progenitor cells (AHPCs) is considered from a mathematical perspective. The proposed mathematical model includes two different mechanisms for stimulation and is based on mass–action kinetics. Both biological mechanisms involve sequential binding, with one pathway solely utilizing surface receptors while the other pathway also involves soluble receptors. Choosing biologically-reasonable values for parameters, simulations of the mathematical model show good agreement with experimental results. A global sensitivity analysis is also conducted to determine both the most influential and non-influential parameters on cellular differentiation, providing additional insights ...

A C9orf72 Bac Mouse Model Recapitulates Key Epigenetic Perturbations Of Als/Ftd, Rustam Esanov, Gabriela Toro Cabrera, Nadja S. Andrade, Tania F. Gendron, Robert H. Brown Jr., Michael Benatar, Claes Wahlestedt, Christian Mueller, Zane Zeier

Pediatric Publications and Presentations

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a fatal and progressive neurodegenerative disorder with identified genetic causes representing a significant minority of all cases. A GGGGCC hexanucleotide repeat expansion (HRE) mutation within the C9ORF72 gene has recently been identified as the most frequent known cause of ALS. The expansion leads to partial heterochromatinization of the locus, yet mutant RNAs and dipeptide repeat proteins (DPRs) are still produced in sufficient quantities to confer neurotoxicity. The levels of these toxic HRE products positively correlate with cellular toxicity and phenotypic severity across multiple disease models. Moreover, the degree of epigenetic repression inversely correlates with ...

Nonlinear Dynamics Of Pulsing Oscillators, Christopher B. Fritz

Student Honors Theses By Year

Many oscillatory systems of great interest exhibit pulsing behavior. The analysis of such oscillators has historically utilized a constant-phase model such as the Kuramoto equation to describe their dynamics. These models accurately describe the behavior of pulsing oscillators on larger timescales, but to not explicitly capture the pulsing nature of the system being analyzed. Indeed, the Kuramoto model and its derivatives abstract the pulsing dynamics and instead use a constantly advancing phase, thereby blurring the specific dynamics in order to fit to an analytically tractable framework. In this thesis, a novel modification is presented by introducing a phase-dependence to the ...

Anti-Inflammatory Effect Of Secoisolariciresinol Diglucoside (Sdg) In Microglia, Kevin B. Seto, Kelly L. Jordan-Sciutto, Beth A. Winkelstein, Bekir Karabucak, Eric J. Granquist

Dental Theses

Secoisolariciresinol diglucoside (SDG) is the main plant lignan in flaxseed and has been thoroughly researched in the past decades due to its unique health properties. SDG has been shown to have therapeutic benefits for an array of diseases including breast and prostate cancer, hyperlipidemia, atherosclerosis, hypertension, diabetes mellitus, and radiation pneumonopathy. With a number of studies recognizing the various health benefits of SDG, few have focused on its potential anti-inflammatory effect and, specifically, its interaction with the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Thus, the aim of this study is to elucidate the interaction between SDG and ...

An Analysis Of Neurogenesis In A Mouse Model Of Chemotherapy Related Cognitive Impairment, Maxwell A. Hennings

Electronic Theses and Dissertations

Cancer patients treated with adjuvant chemotherapy often experience cognitive decline following treatment. This phenomenon, often dubbed “chemo brain” or “chemo fog” is usually temporary, but for a subset of survivors, these cognitive impairments can be long-lasting (>10 years) and negatively affect patients’ quality of life, career performance, and social fulfillment. While it is unclear what neurobiological mechanisms underlie chemotherapy related cognitive impairment, the majority of the animal literature has focused on adult neurogenesis. One process important for neurogenesis is the proliferation of new neurons within the dentate gyrus of the hippocampus. It is evident that many chemotherapy agents can negatively ...

Synaptic Plasticity During Learning, Dustin J. Horn

Honors Theses AY 16/17

Memories are formed and stored inside of neural circuits. Synaptic plasticity is the sum of chemical changes occurring within neurons that affect their ability to communicate with one another. This process includes short term potentiation, early long term potentiation, and late long term potentiation. Dendritic plasticity is governed by actin polymerization and the MAPK pathway. Dendritic spines change their shape, volume, and number within seconds. Activation of NMDA receptors by AMPA receptors causes early long term potentiation in the cell and can change the synaptic strength within circuits. Astrocytes communicate with neurons and play an important role in the development ...

Major Neurotransmitters In The Brain, Amy S. Yu '17

Independent Study

Arguably the most important and powerful organ in the human body, the brain controls virtually everything one does. From chewing gum to running a marathon, the brain dictates one’s physical responses and actions, while also mediating learning, memory, and emotions. These functions are all regulated by neurotransmitter activity in the brain. While the brain works in complex ways, recent discoveries about neurotransmitters allow us to better understand the underlying mechanisms of brain operation. Each neurotransmitter fulfills a distinct role, but they rely on one another to perform certain activities in the brain as well. The purpose of this review ...

The Effect Of Ethanol Consumption And Stress On Brain Derived Neurotrophic Factor And Tropomyosin Receptor Kinase B Expression., Katie Marie Masters

University of Tennessee Honors Thesis Projects

No abstract provided.

A Behavioral Prerequisite For The Genetic Analysis Of Auditory Feature Detection Mechanisms In Female Crickets, Rebecca L. Blisko

Senior Honors Projects

Sexual dimorphism is exhibited across all cricket species and is a central aspect of the mating processes of these insects. Only male crickets possess wing structures and pattern generators in the central nervous system that allow them to produce a mating call that is unique to their species in order to attract conspecific females. Conspecific females possess an auditory feature detection circuit in the central nervous system that is capable of detecting the species-specific frequency and temporal pattern of sound pulses within a male call. In order for dimorphic differences in mating behavior to result in successful continuation of a ...

Cerebral Lactate Metabolism And Memory: Implications For Alzheimer's Disease, Richard Andrew Harris

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by amyloid plaques that are comprised of aggregated amyloid-beta peptides. These toxic proteins promote mitochondrial dysfunction and neuronal cell death. A shift in metabolism away from oxidative phosphorylation and toward aerobic glycolysis, with the concomitant production of lactate, affords neurons a survival advantage against amyloid-beta toxicity. Recent evidence now suggests that aerobic glycolysis in the brain plays a critical role in supporting synaptic plasticity, learning, and memory. However, the role of aerobic glycolysis and lactate metabolism in AD-mediated cognitive decline is unknown. My objective was to test the hypotheses that aerobic ...

Effects Of Dietary Emulsifiers On Vasopressin And Oxytocin In Mice, Krishna Mehta

Georgia State Undergraduate Research Conference

No abstract provided.