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Impairment Of The Glial Phagolysosomal System Drives Prion-Like Propagation Of Huntington’S Disease, Graham Davis

Theses and Dissertations

The ability of glia to tightly regulate neuronal health and homeostasis in the CNS is conserved across species. Yet, despite the ability to degrade protein aggregates, glia are vulnerable to the accumulation of neurotoxic amyloid aggregates during neurodegenerative disease progress, and even exacerbate their spread. A developing narrative highlights glia as a double-edged sword in neurodegenerative diseases: initially capable of dynamically responding to amyloid aggregate-ladened dying neurons but also capable of inducing chronic inflammation and creating seeding-competent amyloid oligomers. Thus, uncovering the mechanisms that allow glia to control aggregate deposition while preventing the neurotoxic effects and seed generation is vital …

Sex-Specific Effects Of Chaperone And Glial Defenses On Experimental Lewy Body Disease, Tarun Bhatia

Electronic Theses and Dissertations

Lewy body disorders are a group of neurodegenerative conditions characterized by the pathological misfolding and aggregation of the abundant protein, α-synuclein. The most common Lewy body disorders are Parkinson’s disease and dementia with Lewy bodies. Apart from ageing, male sex is a major risk factor for Lewy body disorders, as men are at ~1.5-fold higher risk for these diseases than women. Yet, preclinical studies on Lewy body disorders rarely examine sex as a biological variable, and the mechanisms underlying sex-skewedness in disease risk remain undetermined.

Here, we developed a sex-stratified model of Lewy body disorders by exposing primary neurons harvested …

Investigating The Neuroprotective Effects Of Cannabinoids And Insulin-Like Growth Factors On Glia With Induced Inflammation, Caleb Bloodworth

Honors Theses

Chronic inflammation is a driver of numerous neurodegenerative diseases that reduce quality of life for affected individuals. Non-psychoactive cannabinoids have begun to gain more interest in the world of anti-inflammatory medicine for chronically ill patients. Along with these cannabinoids, insulin-like growth factor-1 has been examined for its association with downregulation of inflammation. Our research aimed to investigate how neuroglia are affected by treatment with cannabinoids or IGF-1 in the face of inflammation from HIV-1 protein, Tat, or lipopolysaccharide (LPS). Preliminary studies in our laboratory showed that neither cannabinoids or IGF-1 treatment altered astrocyte morphology or overall astrocyte viability under baseline …

Application Of Confocal Microscopy To Study The Neural Mechanisms Underlying Insect And Rodent Behavior, Christian Michelle Harris

Theses, Dissertations and Capstones

Posture and walking require support of the body weight, which is thought to be detected by sensory receptors in the legs. Specificity in sensory encoding occurs through the morphological properties of the sense organs (numerical distribution, receptor size) and their physiological response characteristics. These studies focus upon campaniform sensilla, receptors that detect forces as strains in the insect exoskeleton. To study the morphology of campaniform sensilla, the sites of mechanotransduction (cuticular caps) were imaged by light and confocal microscopy in four species (stick insects, cockroaches, blow flies and Drosophila). These data indicate that the gradient (range) of cap sizes may …

Disentangling Glial Diversity In Peripheral Nerves At Single Nuclei Resolution, Aldrin Kay Yuen Yim

Arts & Sciences Electronic Theses and Dissertations

The ability to discern gene expression at single cell level is revolutionizing our understanding of both basic biology and human health. Peripheral nerves are essential communicators between the outside world and the CNS, as evidenced by the devastating effects of diseases that disrupt them, such as ALS, Charcot-Marie-Tooth Syndrome and diabetic neuropathy. Understanding peripheral nerve dysfunction at a mechanistic level is of considerable interest due to the increasing prevalence and associated patient care costs of these disorders. Although most research of the peripheral nerve has focused on glial-axonal interactions, the important contributions of other cell types besides Schwann cells, such …

An Evolving Epigenome That Determines Tissue And Cell Specificity, Renee Louise Sears

Arts & Sciences Electronic Theses and Dissertations

Understanding the mechanisms driving phenotypic variation is a major goal of biology that unifies classical genetics with the emerging fields of genomics and epigenomics. Human and mouse share over 90% of genes and global tissue-specific patterns of expression are maintained between the species. Thus, it is hypothesized that gene expression is influenced through distinctive regulation among species in order to account for the unmistakable phenotypic divergence. DNA methylation, histone modifications, open chromatin patterns, transcription factor binding, and other epigenetic factors are all associated with shaping, maintaining, and repressing regulatory regions which in turn coordinate gene expression. It is vital to …

Glial Cell Mechanisms Regulate Alcohol Sedation In Drosophila Melanogaster, Kristen M. Lee

Theses and Dissertations

Approximately 16 million people in America are diagnosed with Alcohol Use Disorder (AUD) but no efficacious medical treatments exist. Alcohol-related behaviors can be studied in model organisms, and changes in these behaviors can be correlated with either (i) a risk for alcohol dependence or (ii) a symptom/feature of AUD itself. Although AUD is a disease of the central nervous system, a majority of research has focused on the neuronal underpinnings, leaving glial contributions largely undescribed. We used Drosophila melanogaster (fruit fly) to identify genes whose expression in glia regulates alcohol sedation. Mammals and Drosophila have conserved behavioral responses to alcohol …

Role Of Mcp-1 And Ccr2 In Ethanol-Induced Damage In The Developing Brain, Kai Zhang

Theses and Dissertations--Pharmacology and Nutritional Sciences

Fetal alcohol spectrum disorders (FASD) are caused by alcohol exposure during pregnancy and is the leading cause of mental retardation. Alcohol exposure during development results in the loss of neurons in the developing brain. The underlying molecular mechanisms are unclear and there currently is no cure for FASD. Ethanol-induced neuronal death is accompanied by neuroinflammation. Chemokine monocyte chemoattractant protein 1 (MCP-1) and its receptor C-C chemokine receptor type 2 (CCR2) are critical mediators of neuroinflammation and microglial activation. Using a third trimester equivalent mouse model of ethanol exposure, we found that treatment of Bindarit (MCP-1 synthesis inhibitor) and RS504393 (CCR2 …

Differentiation Of Neurons And Glia For Use In Cellular Connectomics, Jacob T. Brettin

Chancellor’s Honors Program Projects

No abstract provided.

Collective Chemotaxis Of Retinal Neural Cells From Drosophila Melanogaster In Controlled Microenvironments, Stephanie Zhang

Dissertations and Theses

More than 172 million people are influenced by a retinal disorder that stems from either age-related or developmental causes. Of those, 1.5 million people endure a developmental retinal disorder. In the developing retina, neural cells undergo a series of highly complicated differentiation and migration process. A main cause of these diseases is abnormal collective migration of neural progenitors hindering the retinogenesis process. However, our grasp of collective migration and signaling molecules, critical to the developing retina, is incompletely understood. Understanding the molecular mechanisms, such as the fibroblast growth factor pathway, that regulate glial and neuronal migration provides decisive insights in …

Defining The Immune Response And Cellular Pathologies In Multiple System Atrophy, Annamarie Valenti

Masters Theses

Multiple System Atrophy (MSA) is a neurodegenerative disease characterized by the accumulation of misfolded α-synuclein (α-Syn) in oligodendrocytes of the central nervous system (CNS). A previous study in our lab used Affymetrix DNA microarray analysis to show the downregulation of various mitochondrial related genes, as well as the upregulation of genes involved in inflammatory/immune responses in MSA brain tissue. Therefore, it is hypothesized that an increased presence of immune proteins exists in the MSA brain accompanied by glial cell pathology including decreases in cell metabolism and cell viability. This study uses immunohistochemistry (IHC) to show the increased presence of CD68 …

Mtor Signaling And Endoplasmic Reticulum Stress In Mixed Glial Cultures, William Theodore Schreiber-Stainthorp

Senior Theses and Projects

Oligodendrocytes are the myelinating cells of the central nervous system. The extraordinary protein and lipid synthesis that myelin production entails makes oligodendrocytes especially prone to endoplasmic reticulum (ER) stress. In this experiment, we set out to investigate the dynamics of ER stress in mixed glial cultures, and how the consequences of that stress vary based on the activity of the anabolic PI3K/AKT/mTOR pathway. Previous experiments in isolated oligodendrocyte cultures demonstrated a negative correlation between AKT/mTOR signaling and oligodendrocyte cell viability in the presence of ER stressors. Because ER stress leads to a buildup of improperly processed proteins, decreases in mTOR …

Autoregulation Of The Glial Gene Reversed Polarity In Drosophila Melanogaster, Jamie L. Wood

Electronic Theses and Dissertations

During development, cells of the nervous system begin as unspecified precursors and proceed along one of two developmental paths to become either neurons or glia. I seek to understand more about the genes that control this process, focusing on the lesser understood of the cell types, glial cells. Using Drosophila melanogaster as a model system, previous work from my lab and others has established the role of the master regulatory transcription factor Gcm in directing neuronal precursor cells to assume a lateral glial fate. Gcm acts on many target genes, one of which is reversed polarity (repo). repo is necessary …

Role Of Glia Subsets In Neurodegeneration And Life Span Reduction; Gain-Of-Function Phenotypes Following Glia Specific Overexpression Of Rap/Fzr, An Activator Of The Anaphase-Promoting Complex, Amandeep Kaur

Dissertations and Theses

No abstract provided.

Glia-Mediated Neurodegeneration In The Drosophila Melanogaster Cns, Ivan J. Santiago

Dissertations and Theses

No abstract provided.

Morphological And Neuroanatomical Changes Associated With The Induction Of Neurodegeneration And Life Span Reduction In Drosophila Melanogaster By Glia Targeted Expression Of Cdh1/Rap/Fzr, An Activator Of The Anaphase Promoting Complex, Israel Nnah

Dissertations and Theses

"The retina aberrant in pattern (rap) gene encodes the Fizzy-related protein (Fzr), an activator of the E3 ubiquitin ligase complex: the Anaphase Promoting Complex/Cyclosome (APC/C). APC/C facilitates the cell cycle stage-specific degradation of cyclins and other mitotic regulators, resulting in the inactivation of Cdk (Cyclin Dependent Kinase) complexes, thus promoting completion of mitosis. Previous studies from our laboratory have shown that Rap/Fzr (the Drosophila homolog of the mammalian Cdh1) regulates glia differentiation and promotes neuron formation. Recent studies have shown that the glia specific over expression of Rap/Fzr causes progressive neurodegeneration and life span reduction preceded by temperature sensitive paralysis, …

Glia Are Required For Sensory Neuron Morphology And Function In Caenorhabditis Elegans, Taulant Bacaj

Student Theses and Dissertations

The nervous system emerges from the coordinated development of neurons and glia. To better understand the processes that enable nervous system development and function we have studied the sensory organs of Caenorhabditis elegans because their anatomy and function are well-characterized. Specifically, we have focused on two aspects of sensory organs: how do glia interact with neurons to enable proper development and function and how are sensory cilia generated. To uncover any glial roles, we ablated the major glial cell of the amphid sensilla. Embryonic glial ablation did not affect neuronal survival and resulted in sensory neuron dendrites that were far …