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Hiv-1 Tat Interactions With Opioids Are Modulated By Progesterone And Estradiol, Dejun Jackson 2020 University of Mississippi

Hiv-1 Tat Interactions With Opioids Are Modulated By Progesterone And Estradiol, Dejun Jackson

Honors Theses

HIV infection and combined substance abuse are comorbid epidemics. Previous studies show that concurrent opioid drug use may potentiate HIV-1-mediated neurotoxicity partly via interactions with opioids. Preclinical studies suggest that the HIV-1 trans-activator of transcription (Tat), an HIV regulatory protein, can synergize with opioids to exacerbate its already neurotoxic effects. However, its interactions with clinical opioids, such as oxycodone, have yet to be elucidated. Additionally, Tat disrupts a number of systems including the dopaminergic system, which contribute to its capacity to potentiate the rewarding effects of abused drugs. Although the neurotoxic effects of Tat may be inhibited by gonadal steroids ...


Neuroligin3 Splice Isoforms Shape Inhibitory Synaptic Function In The Mouse Hippocampus, Motokazu Uchigashima, Ming Leung, Takuya Watanabe, Amy Cheung, Timmy Le, Sabine Pallat, Alexandre Luis Marques Dinis, Masahiko Watanabe, Yuka Imamura Kawasawa, Kensuke Futai 2020 University of Massachusetts Medical School

Neuroligin3 Splice Isoforms Shape Inhibitory Synaptic Function In The Mouse Hippocampus, Motokazu Uchigashima, Ming Leung, Takuya Watanabe, Amy Cheung, Timmy Le, Sabine Pallat, Alexandre Luis Marques Dinis, Masahiko Watanabe, Yuka Imamura Kawasawa, Kensuke Futai

Open Access Publications by UMMS Authors

Synapse formation is a dynamic process essential for the development and maturation of the neuronal circuitry in the brain. At the synaptic cleft, transsynaptic protein-protein interactions are major biological determinants of proper synapse efficacy. The balance of excitatory and inhibitory synaptic transmission (E-I balance) stabilizes synaptic activity, and dysregulation of the E-I balance has been implicated in neurodevelopmental disorders, including autism spectrum disorders. However, the molecular mechanisms underlying the E-I balance remain to be elucidated. Here, using single-cell transcriptomics, immunohistochemistry and electrophysiology approaches to murine CA1 pyramidal neurons obtained from organotypic hippocampal slice cultures, we investigate Neuroligin (Nlgn) genes that ...


The Current Neuroscientific Understanding Of Alzheimer's Disease, Rachel A. Brandes 2020 University of Tennessee, Knoxville

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 ...


Neurocognitive Risk Factors And Current Intervention Strategies For Survivors Of Pediatric Acute Lymphoblastic Leukemia, Abigail Taber 2020 Liberty University

Neurocognitive Risk Factors And Current Intervention Strategies For Survivors Of Pediatric Acute Lymphoblastic Leukemia, Abigail Taber

Senior Honors Theses

The improved survival rate for pediatric cancer patients is one of the greatest triumphs of recent medicine, but the late effects faced by these survivors have been uncovered through this new population of survivors. Many survivors of pediatric acute lymphoblastic leukemia (ALL) experience cognitive deficits in areas such as attention, memory, processing speed, and academic achievement following cancer treatment. Recent research has pointed to chemotherapeutic agents, host risk factors, and genetic predispositions as perpetrators of these deficits, although other factors are also under investigation. Consequently, the search for appropriate interventions for the amelioration of these deficits has dominated the literature ...


A Study Of Matr3 And Its Effects On The Neural Progenitor Cells Of Xenopus Laevis Tadpoles, Kendall Branham 2020 William & Mary

A Study Of Matr3 And Its Effects On The Neural Progenitor Cells Of Xenopus Laevis Tadpoles, Kendall Branham

Undergraduate Honors Theses

Understanding the genes and mechanisms that regulate the highly important process of neurogenesis in the developing nervous system is crucial to uncovering why disease arises when this system is disrupted. Neural progenitor cells and their multipotent nature allow for the growth of a large pool of stem cells in the early stages of development, but the signal that leads these cells to the irreversible fate of becoming a neuron is unclear. The gene matr3 has been implicated in having a role in the maintenance of undifferentiated neural stem cells but its role needs further investigation to fully reveal how its ...


The Role Of Dopamine In Decision Making Processes In Drosophila Melanogaster, Michelle C. Bowers 2020 University of San Diego

The Role Of Dopamine In Decision Making Processes In Drosophila Melanogaster, Michelle C. Bowers

Undergraduate Honors Theses

Understanding the neural processes that mediate decision making is a relatively new field of investigation in the scientific community. With the ultimate goal of understanding how humans decide between one path and another, simpler models such as Drosophila Melanogaster, the common fruit fly, are often utilized as a way of determining the neural circuits involved in these decision-making processes. One of the most important decisions flies make is the decision of where to lay their eggs (oviposit). Choosing the proper substrate upon which to lay eggs is a crucial decision that can ultimately impact their fecundity. This paper investigates the ...


The Functional Role Of Mitochondria In Neural Progenitor Cells, Alyssa Luz-Ricca 2020 William & Mary

The Functional Role Of Mitochondria In Neural Progenitor Cells, Alyssa Luz-Ricca

Undergraduate Honors Theses

Neurodevelopment is a complex process that requires the precise spatiotemporal control of cellular differentiation. As cells differentiate, they undergo metabolic changes that make them increasingly reliant on their mitochondria for energy production. Beyond playing a central role in the bioenergetic support of newborn neurons, functional changes in mitochondria regulate the processes of cellular differentiation. Importantly, mitochondrial function extends beyond energy production. Mitochondria in neural stem cells play an essential role in both producing intermediates for biosynthesis and regulating calcium levels. In this thesis, I review the functional role of mitochondria in stem cell fate decisions, differentiation, and proliferation during neurodevelopment ...


Rit2-Dependent Dopamine Transporter Endocytosis: Intrinsic Mechanism And In Vivo Impact, Rita R. Fagan 2020 University of Massachusetts Medical School

Rit2-Dependent Dopamine Transporter Endocytosis: Intrinsic Mechanism And In Vivo Impact, Rita R. Fagan

GSBS Dissertations and Theses

Dopamine (DA) governs movement, sleep, reward, and cognition. The presynaptic dopamine transporter (DAT), clears released DA, controlling DA signaling and homeostasis. Genetic DAT ablation causes hyperactivity, sleep reduction, and altered psychostimulant response. DAT surface expression is dynamic; DAT constitutively internalizes and recycles to and from the plasma membrane, and acute PKC activation stimulates DAT endocytosis. Cell line experiments demonstrated that PKC-stimulated DAT endocytosis requires Ack1 inactivation and the GTPase, Rit2. How Rit2 controls PKC-dependent DAT internalization, or whether regulated DAT endocytosis impacts behavior, is unknown. Here, I present data supporting that PKC activation stimulates Rit2/DAT dissociation, mediated by the ...


Beta-Endorphin Expression And Sex Affect The Ability Of Alcohol To Alter Tyrosine Hydroxylase Immunoreactivity In The Reward Pathway In Mice, Hannah Kelly-Quigley 2020 Susquehanna University

Beta-Endorphin Expression And Sex Affect The Ability Of Alcohol To Alter Tyrosine Hydroxylase Immunoreactivity In The Reward Pathway In Mice, Hannah Kelly-Quigley

Senior Scholars Day

Alcohol has sexually dimorphic effects on the brain, and the endogenous opioid, beta-endorphin (BE), mediates many effects of alcohol. In the mesolimbic dopamine reward pathway, alcohol stimulates neurons to enhance dopaminergic signaling, but the exact mechanism underlying this phenomenon is unknown. Alcohol could impact dopaminergic signaling in the reward pathway by affecting the production and localization of tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine synthesis. Therefore, we hypothesized that acute alcohol intoxication would increase c-fos expression and tyrosine hydroxylase immunoreactivity (TH-ir) in the ventral tegmental area (VTA) and nucleus accumbens (NAc) in a sex- and BE-dependent manner. In this ...


The Role Of Diet In The Onset Of Depression: A Biochemical Connection Between Nutrition And Mental Health, Katlin Wildeman 2020 Liberty University

The Role Of Diet In The Onset Of Depression: A Biochemical Connection Between Nutrition And Mental Health, Katlin Wildeman

Senior Honors Theses

Depression is a major clinical concern, having a complex onset and the presence of multiple, often unidentifiable causes. Depression affects millions of individuals worldwide, with a high prevalence in regions of the world with a Western-style diet as compared to regions with a Mediterranean diet. A Western-style diet consists of foods high in sugar, fat, and processed meats and grains, whereas the Mediterranean diet contains significantly more vegetables, fruits, lean meats, and whole grains. The link between diet and mental health disorders has implications for individuals of all ages who are hesitant to turn to medication. In addition to presenting ...


Polyglucosan Body Structure In Lafora Disease, M. Kathryn Brewer, Jean-Luc Putaux, Alberto Rondon, Annette M. Uittenbogaard, Mitchell A. Sullivan, Matthew S. Gentry 2020 University of Kentucky

Polyglucosan Body Structure In Lafora Disease, M. Kathryn Brewer, Jean-Luc Putaux, Alberto Rondon, Annette M. Uittenbogaard, Mitchell A. Sullivan, Matthew S. Gentry

Lafora Epilepsy Cure Initiative Faculty Publications

Abnormal carbohydrate structures known as polyglucosan bodies (PGBs) are associated with neurodegenerative disorders, glycogen storage diseases (GSDs), and aging. A hallmark of the GSD Lafora disease (LD), a fatal childhood epilepsy caused by recessive mutations in the EPM2A or EPM2B genes, are cytoplasmic PGBs known as Lafora bodies (LBs). LBs result from aberrant glycogen metabolism and drive disease progression. They are abundant in brain, muscle and heart of LD patients and Epm2a-/- and Epm2b-/- mice. LBs and PGBs are histologically reminiscent of starch, semicrystalline carbohydrates synthesized for glucose storage in plants. In this study, we define LB architecture, tissue-specific differences ...


Effect Of Reduced Neurogenesis On Microglial Activation, Amelia Smith 2020 Belmont University

Effect Of Reduced Neurogenesis On Microglial Activation, Amelia Smith

Honors Theses

The geriatric population of America has grown exponentially in the past century. Health degradations and expensive medical care are characteristic of this population with many of these costs due to age-related cognitive decline. It is essential to completely understand the mechanisms of normal and abnormal aging in the search for treatments for cognitive decline. A reduction of neurogenesis is a common factor in aging, but this reduction is even more drastic in individuals experiencing cognitive decline. It is unclear what effect reduced neurogenesis has on the extracellular environment, including glial cells. In particular, changes in microglial activation could be related ...


Serum-Based Biomarkers And Magnetic Resonance Imaging Following Mild Traumatic Brain Injury In Collegiate Athletes Post Return-To-Play, Taylor R. Susa 2020 Northern Michigan University

Serum-Based Biomarkers And Magnetic Resonance Imaging Following Mild Traumatic Brain Injury In Collegiate Athletes Post Return-To-Play, Taylor R. Susa

All NMU Master's Theses

Recently there has been an increase in the use of MRI (Magnetic Resonance Imaging), to measure the effects of traumatic brain injury (TBI). Proteins such as BDNF, S100B, UCH-L1, and Tau have been found to have altered levels in blood serum after TBI. However, there is limited knowledge about the relationship between serum-based and MRI-based biomarkers in concussed athletes post return-to-play. This study aimed to bridge this gap by collecting serum samples from 42 participants across two groups. The first group (n = 21) consisted of recently cleared to return-to-play collegiate athletes after experiencing a sports-related concussion. The second group (n ...


Amino Acid Sensing Ability By The Mechanistic Target Of Rapamycin In Oligodendrocytes, Emma England 2020 Trinity College

Amino Acid Sensing Ability By The Mechanistic Target Of Rapamycin In Oligodendrocytes, Emma England

Senior Theses and Projects

Oligodendrocytes (OLs) are a type of glial cell in the central nervous system that require substantial nutrients such as lipids and amino acids to create the extensive, metabolically expensive myelin sheath surrounding the axons of neurons. The mammalian target of rapamycin (mTOR) is a regulatory kinase that is necessary for the maturation of progenitor OLs through their distinct oligo-lineage phases. Amino acids are vital for the functioning of cells. The focus of this study was to determine if mTOR activity is dependent on the availability of leucine, methionine, and alanine. This was assessed by examining the phosphorylation level of the ...


The Expression Of Mtor And Trib3 In Oligodendrocyte Lineage Cells, Katie Lazur 2020 Trinity College

The Expression Of Mtor And Trib3 In Oligodendrocyte Lineage Cells, Katie Lazur

Senior Theses and Projects

Oligodendrocytes are a type of glial cell in the central nervous system that are responsible for producing the myelin sheath which allows for faster neuronal firing rates. Myelin production is a metabolically expensive process, which requires the oligodendrocytes to be aware of the nutrients are available to them. It has been demonstrated that the mammalian target of Rapamycin (mTOR) is required for the later stages of maturation in oligodendrocytes. However, when mTOR is inhibited by Rapamycin in the early stages of oligodendrocyte development, the oligodendrocytes are still able to fully differentiate. Tribbles Homolog 3 (Trib3) is a pseudo kinase that ...


Beta-Amyloid Clustering Around Asc Fibrils Boosts Its Toxicity In Microglia, Lea L. Friker, Hannah Scheiblich, Inga V. Hochheiser, Rebecca Brinkschulte, Dietmar Riedel, Eicke Latz, Matthias Geyer, Michael T. Heneka 2020 University of Bonn Medical Center

Beta-Amyloid Clustering Around Asc Fibrils Boosts Its Toxicity In Microglia, Lea L. Friker, Hannah Scheiblich, Inga V. Hochheiser, Rebecca Brinkschulte, Dietmar Riedel, Eicke Latz, Matthias Geyer, Michael T. Heneka

Open Access Publications by UMMS Authors

Alzheimer's disease is the world's most common neurodegenerative disorder. It is associated with neuroinflammation involving activation of microglia by beta-amyloid (Abeta) deposits. Based on previous studies showing apoptosis-associated speck-like protein containing a CARD (ASC) binding and cross-seeding extracellular Abeta, we investigate the propagation of ASC between primary microglia and the effects of ASC-Abeta composites on microglial inflammasomes and function. Indeed, ASC released by a pyroptotic cell can be functionally built into the neighboring microglia NOD-like receptor protein (NLRP3) inflammasome. Compared with protein-only application, exposure to ASC-Abeta composites amplifies the proinflammatory response, resulting in pyroptotic cell death, setting free ...


Premature Termination Codon Readthrough Upregulates Progranulin Expression And Improves Lysosomal Function In Preclinical Models Of Grn Deficiency, Jonathan Frew, Fen-Biao Gao, Haakon B. Nygaard 2020 University of British Columbia

Premature Termination Codon Readthrough Upregulates Progranulin Expression And Improves Lysosomal Function In Preclinical Models Of Grn Deficiency, Jonathan Frew, Fen-Biao Gao, Haakon B. Nygaard

Open Access Publications by UMMS Authors

BACKGROUND: Frontotemporal lobar degeneration (FTLD) is a devastating and progressive disorder, and a common cause of early onset dementia. Progranulin (PGRN) haploinsufficiency due to autosomal dominant mutations in the progranulin gene (GRN) is an important cause of FTLD (FTLD-GRN), and nearly a quarter of these genetic cases are due to a nonsense mutation. Premature termination codons (PTC) can be therapeutically targeted by compounds allowing readthrough, and aminoglycoside antibiotics are known to be potent PTC readthrough drugs. Restoring endogenous PGRN through PTC readthrough has not previously been explored as a therapeutic intervention in FTLD.

METHODS: We studied whether the aminoglycoside G418 ...


A Chromosomal Connectome For Psychiatric And Metabolic Risk Variants In Adult Dopaminergic Neurons, Sergio Espeso-Gil, Tyler M. Borrman, Zhiping Weng, Schahram Akbarian 2020 Icahn School of Medicine at Mount Sinai

A Chromosomal Connectome For Psychiatric And Metabolic Risk Variants In Adult Dopaminergic Neurons, Sergio Espeso-Gil, Tyler M. Borrman, Zhiping Weng, Schahram Akbarian

Open Access Publications by UMMS Authors

BACKGROUND: Midbrain dopaminergic neurons (MDN) represent 0.0005% of the brain's neuronal population and mediate cognition, food intake, and metabolism. MDN are also posited to underlay the neurobiological dysfunction of schizophrenia (SCZ), a severe neuropsychiatric disorder that is characterized by psychosis as well as multifactorial medical co-morbidities, including metabolic disease, contributing to markedly increased morbidity and mortality. Paradoxically, however, the genetic risk sequences of psychosis and traits associated with metabolic disease, such as body mass, show very limited overlap.

METHODS: We investigated the genomic interaction of SCZ with medical conditions and traits, including body mass index (BMI), by exploring ...


Mushroom Body-Specific Gene Regulation By The Swi/Snf Chromatin Remodeling Complex, Kevin CJ Nixon 2020 The University of Western Ontario

Mushroom Body-Specific Gene Regulation By The Swi/Snf Chromatin Remodeling Complex, Kevin Cj Nixon

Electronic Thesis and Dissertation Repository

Over the lifetime of an organism, neurons must establish, remodel, and maintain precise connections in order to form neural circuits that are required for proper nervous system functioning. Disruptions in these processes can lead to neurodevelopmental disorders such as intellectual disability (ID) and autism spectrum disorder. Mutations in genes encoding subunits of the SWI/SNF chromatin remodeling complex have been implicated in ID, yet the role of this complex in neurons is poorly understood. In this project, I established cell-type specific methods to examine the effect of SWI/SNF subunit knockdowns on gene transcription and chromatin structure in the memory-forming ...


Tamalin/Gras-1 Connects Glutamate Receptor Activity To The Insulin/Igf Signaling Cascade To Regulate Neuroprotection In A Nematode Model Of Excitotoxicity, Ayesha Chowdhury 2020 The Graduate Center, City University of New York

Tamalin/Gras-1 Connects Glutamate Receptor Activity To The Insulin/Igf Signaling Cascade To Regulate Neuroprotection In A Nematode Model Of Excitotoxicity, Ayesha Chowdhury

Dissertations, Theses, and Capstone Projects

Brain ischemia is a major cause of debilitation and death in the United States. Excitotoxicity, a condition that arises from the accumulation of glutamate (Glu) in the synapse that leads to overactivation of Glu receptors (GluRs), is the major mechanism of neuronal damage in brain ischemia / stroke. Although it is commonly acknowledged that over activation of GluRs leads to neurodegeneration, it has been recently shown that even during excitotoxicity Glu has a concurrent important role in regulating neuroprotection. GluR-activated transcription factors seem to mediate this neuroprotection, but it remains unclear which signaling cascades and transcription factors are regulated by GluRs ...


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