Neuroscience and Neurobiology Commons^™

Qki-Mediated Cholesterol Biosynthesis In Eye Lens And Myelin Of The Central Nervous System, Seula Shin, Seula Shin

Dissertations & Theses (Open Access)

Cells obtain cholesterol in two ways, de novo biosynthesis and uptake from circulation. While most tissues utilize both sources, eye lens and brain depend extensively on cholesterol biosynthesis due to the limited supply from circulation. Lens cell membrane consists of highest portion of cholesterol. Brain is the most cholesterol-rich organ, which accounts for 23% of total cholesterol. Genetic mutations of cholesterol biosynthesis enzymes in humans and animal models present cataracts and hypomyelinating disorders linked to neurological impairment. Yet, it remains unclear how gene expression of cholesterol biosynthesis is regulated in lens and brain. Therefore, studying cholesterol biosynthesis in both tissues …

Calcium Dyshomeostasis In Neurodegeneration, Nicholas Emanuel Karagas

Dissertations & Theses (Open Access)

Neurodegenerative diseases, despite constituting a major and growing cause of mortality globally, have few effective treatments. In order to develop novel therapeutics to combat neurodegeneration, a better understanding of the molecular mechanisms underlying these diseases is needed. Neurons rely on Ca²⁺ to mediate many of their unique functions, and aberrant Ca²⁺ signaling has been broadly implicated in neurodegeneration. The goal of this dissertation is to delineate specific examples of Ca²⁺ dyshomeostasis that I have uncovered in Drosophila models of neurodegeneration.

I first define the role a neurodegeneration-associated mutation plays in perturbing presynaptic [Ca²⁺], which is …

A Two-Clone Approach To Study Signaling Interactions Among Neuronal Cells In A Pre-Clinical Alzheimer’S Disease Model, Catherine J. Yeates, Ankita Sarkar, Prajakta Deshpande, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

To understand the progression of Alzheimer's disease, studies often rely on ectopic expression of amyloid-beta 42 (Aβ42) throughout an entire tissue. Uniform ectopic expression of Aβ42 may obscure cell-cell interactions that contribute to the progression of the disease. We developed a two-clone system to study the signaling cross talk between GFP-labeled clones of Aβ42-expressing neurons and wild-type neurons simultaneously generated from the same progenitor cell by a single recombination event. Surprisingly, wild-type clones are reduced in size as compared with Aβ42-producing clones. We found that wild-type cells are eliminated by the induction of cell death. Furthermore, aberrant activation of c-Jun-N-terminal …

Qki-Mediated Cholesterol Biosynthesis In Eye Lens And Myelin Of The Central Nervous System, Seula Shin, Seula Shin

Dissertations & Theses (Open Access)

Cells obtain cholesterol in two ways, de novo biosynthesis and uptake from circulation. While most tissues utilize both sources, eye lens and brain depend extensively on cholesterol biosynthesis due to the limited supply from circulation. Lens cell membrane consists of highest portion of cholesterol. Brain is the most cholesterol-rich organ, which accounts for 23% of total cholesterol. Genetic mutations of cholesterol biosynthesis enzymes in humans and animal models present cataracts and hypomyelinating disorders linked to neurological impairment. Yet, it remains unclear how gene expression of cholesterol biosynthesis is regulated in lens and brain. Therefore, studying cholesterol biosynthesis in both tissues …

Comparative Efficacies Of Calmare Therapy And Transcutaneous Electrical Nerve Stimulation In Randomized Peripheral Neuropathy Subjects With Resting State Fmri Monitoring, Ty A. Bodily, Logan Edvalson, Jordan B. Peacock, Zack M. Bradshaw, Carson Hart, Cameron Ernst, Samuel Biggs, David D. Busath

Faculty Publications

Clinical reports of Calmare protocol efficacy suggest enhanced durability compared to TENS and the possibility changes in resting fMRI connectivity. The objective was to compare peripheral neuropathy pain relief and resting fMRI changes with Calmare and TENS treatments. Randomized double-blind trials performed in August 2015 and between August 2016 and November 2017, with 18 and 20 human peripheral neuropathy subjects, respectively. The initial trial examined effects of a single session while the latter trial examined the effects of a course of ten treatment sessions on consecutive weekdays. fMRI scans were examined for changes in blood flow correlations and connectivity. Subjective …

Dnajc7, A Molecular Chaperone Protein That Modulates Protein Misfolding In Amyotrophic Lateral Sclerosis (Als), Meaghan Kathleen Stoltz

Electronic Thesis and Dissertation Repository

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease associated with protein misfolding and dysregulated cellular protein quality control mechanisms. Molecular chaperones, and heat shock proteins (Hsp), are key players in maintaining cellular protein quality control. DNAJC7 is an understudied cytosolic Hsp40 that works together with Hsp70 and Hsp90 to regulate proper protein folding or degradation. Of note, mutations in the gene encoding DNAJC7 were discovered to cause familial ALS. We asked whether ALS-associated mutations in DNAJC7 compromise its function as a chaperone, which may cause the toxic accumulation of misfolded proteins. This study attempts to uncover the functions of DNAJC7 …

Delineating The Role Of Mir-124 For The Activation Of Neuronal Program, Ya-Lin Lu

Arts & Sciences Electronic Theses and Dissertations

The ectopic expression of two brain-enriched microRNAs (miRNAs), miR-9/9* and miR-124 (miR-9/9*-124), can robustly and efficiently reprogram human skin fibroblasts into neurons. The miRNAs act as repressors of non-neuronal genes in fibroblasts for the induction of the neuronal program. This process is analogous to neurogenesis in vivo when the expression of miR-9/9* and miR-124 represses anti-neurogenic genes such as REST or NRSF (neuron-restrictive silencer factor/repressor element-1 silencing transcription factor). Although we have some mechanistic insights into how miR-9/9*-124 drives fate conversion by acting as negative regulators of gene expression, little remained understood of the role of miRNAs as positive regulators …

Effect Of S100b Deletion On Membrane Properties And Localization Of Ncald And Hpca, Natasha Hesketh

Graduate School of Biomedical Sciences Theses and Dissertations

Calcium signaling is particularly important for neuronal function. Neurons utilize a wide range of calcium-binding proteins. Dysregulation of such proteins is linked to neurodegeneration. Neurocalcin delta (NCALD), hippocalcin (HPCA), and S100B are calcium sensors that are expressed in the hippocampus, a brain region essential to memory and severely damaged in Alzheimer’s disease (AD). Despite the potential importance of these proteins, we do not fully understand the physiological significance of their relationship. Because NCALD and HPCA are known to interact with S100B, we hypothesized that the loss of S100B affects NCALD and HPCA localization, and therefore electrical properties, of hippocampal neurons. …

Gene Regulation And Cell Fate Choice In The Developing Vertebrate Retina, Sruti Patoori

Dissertations, Theses, and Capstone Projects

The diverse neuronal cell types in the vertebrate retina all originate from multipotent retinal progenitor cells (RPCs). These undergo a series of molecular changes driven by developmental gene regulatory networks (GRNs) as they divide to generate RPCs which are more restricted in their potential fates. It is crucial to understand these GRNs and changes to gene expression in order to understand how cell identity is established during retinal development. In particular, the GRN that promotes the development of cone photoreceptors and horizontal cells is not well-defined. This work focuses on two approaches to further elucidate the components of this regulatory …

Emergence, Mechanics, And Development: How Behavior And Geometry Underlie Cowrie Seashell Form, Michael G. Levy, Michael R. Deweese

Biology and Medicine Through Mathematics Conference

No abstract provided.

Transcriptional And Epigenetic Regulation Of Cerebellar Development And Function, Naveen C. Reddy

Arts & Sciences Electronic Theses and Dissertations

Precise control of gene expression is essential for neural development and function. This control is regulated by the interplay of chromatin remodelers and transcription factors (TFs). To better understand these mechanisms involved in gene regulation, we pursue two questions: 1) what are the roles of the chromatin remodeler CHD7 in cerebellar development and 2) what are the roles of the MEF2 TF family in cerebellar function. CHD7 mutations are causative for CHARGE syndrome, a heterogeneous disorder affecting many organ systems, occurring in 1:10,000 newborns. Recent MRI studies have identified cerebellar hypoplasia and foliation defects in a large portion of CHARGE …

Fgf20 In Olfactory System And Cochlea Development, Lu Morgan Yang

Arts & Sciences Electronic Theses and Dissertations

The olfactory epithelium (OE) is a neurosensory organ required for the sense of smell. Turbinates, bony projections from the nasal cavity wall, increase the surface area within the nasal cavity lined by the OE. We identified a population of OE progenitor cells that expand horizontally during development to populate all lineages of the mature OE and increase OE surface area. We show that these Fgf20-positive, epithelium-spanning progenitor (FEP) cells are responsive to Wnt/β-Catenin signaling. Wnt signaling suppresses FEP cell differentiation into OE basal progenitors and their progeny, and positively regulates Fgf20 expression. We further show that FGF20 signals to the …

Expression Analyses Of Hippocampal And Cortical Proteins In A Rat Model For Alzheimer’S Disease, Rangon Islam

Theses and Dissertations

Currently, Alzheimer’s disease (AD) has no cure. Using a rat AD model, we identified aberrantly expressed proteins during pre-pathology as potential biomarkers. The expression of certain biomarkers was reversed by diazoxide, a repurposed hypertension drug. These results suggest that drug repurposing at an early stage of AD has therapeutic potential.

Sexually Dimorphic Alterations In Brain Morphology Of Astrocyte Conditional System Xc- Knockout Mice, Gabrielle Emily Samulewicz

Biology - All Scholarship

Astrocytes play a vital role in orchestrating the precise brain wiring that occurs during development and are essential for maintaining homeostasis into adulthood. The cystine/glutamate antiporter, system xc-, in the central nervous system is especially abundant in astrocytes and itself is known to contribute importantly to the basal extracellular glutamate concentration as well as the intracellular and extracellular glutathione levels, either of which, if perturbed, could alter brain development and/or contribute to degeneration. Thus, to determine whether loss of astrocyte system xc- might alter brain morphology, I studied a conditional astrocyte system xc- knockout mouse (AcKO). Tissue was harvested from …

Sexually Dimorphic Alterations In Brain Morphology Of Astrocyte Conditional System Xc- Knockout Mice, Gabrielle Emily Samulewicz

Honors Capstone Projects - All

Astrocytes play a vital role in orchestrating the precise brain wiring that occurs during development and are essential for maintaining homeostasis into adulthood. The cystine/glutamate antiporter, system xc-, in the central nervous system is especially abundant in astrocytes and itself is known to contribute importantly to the basal extracellular glutamate concentration as well as the intracellular and extracellular glutathione levels, either of which, if perturbed, could alter brain development and/or contribute to degeneration. Thus, to determine whether loss of astrocyte system xc- might alter brain morphology, I studied a conditional astrocyte system xc- knockout mouse (AcKO). Tissue was harvested from …

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 …

Microglia-Neuron Interactions In A Mouse Model Of Low Grade Neuroepithelial Tumors, Veolette Hanna

Honors Scholar Theses

Microglia are the macrophages of the brain and spinal cord, playing an important role in the immune response to disease states of the nervous system. This study conducts an investigation on the activity of microglia in response to low grade neuroepithelial tumors. Using mouse models and microglial markers, a qualitative and quantitative analysis of microglia activation, migration, and invasion within the brain cortex during early stages of tumor development was conducted. It was found that the presence of a low grade neuroepithelial tumor in the cortex of one hemisphere of the brain causes significant microglia activation in comparison to the …

Elucidation Of The Mechanisms By Which Anesthetics Induce Blood-Brain Barrier Breakdown And Delirium In The Elderly, George A. Godsey Ii

Graduate School of Biomedical Sciences Theses and Dissertations

Delirium is a highly prevalent neuropsychiatric or neurocognitive disorder that presents a major problem to modern healthcare. Patients suffering from delirium normally have a worse prognosis, prolonged hospital stay, increased hospital cost, long-term cognitive impairment, and higher mortality rates. Many factors can predispose one to develop delirium, which makes treating this disorder a daunting task. Unfortunately, delirium is the most common psychiatric syndrome found in the hospital setting. In fact, a form of delirium known as postoperative delirium (POD) is one of the most common postoperative complications faced by elderly patients undergoing surgery.

POD is a major problem in modern …

The Effect Of Hypoxia On Brain Cell Proliferation In Weakly Electric Fish, Petrocephalus Degeni, Kaitlin Klovdahl

Senior Theses and Projects

Oxygen levels tend to remain at a steady state concentration in the Earth’s atmosphere, yet in some bodies of water, they can fluctuate and decrease drastically. Many organisms that inhabit the swamps, lakes, streams, and parts of the ocean where this occurs have evolved adaptations to manage this environmental uncertainty and continue normal oxygen consumption. The Lwamunda swamp in Uganda is chronically hypoxic, yet it is home to many species, including the electric fish Petrocephalus degeni. P. degeni are unusual by nature of their immense brain, and the Lwamunda swamp appears ill-suited for maintaining this large, metabolically active organ. To …

Thyroxine-Dependent And -Independent Effects On Premature Aging And Myelination In Atrx Mutant Mice, Megan E. Rowland

Electronic Thesis and Dissertation Repository

ATRX is an ATP-dependent chromatin remodeler required to safeguard genomic integrity. Conditional deletion of Atrx in the mouse embryonic forebrain and anterior pituitary in Atrx^Foxg1Cre mice phenocopies mouse models of progeria which display increased DNA damage, coupled with reduced lifespan, growth and subcutaneous fat. These mice also have severely low circulating levels of insulin like growth factor 1 (IGF-1) and (T4) which have been reported in models of premature aging. Based on evidence that Igf1 is activated by the ligand-bound thyroid hormone receptor, I tested whether T4 supplementation could restore IGF-1 levels and ameliorate premature aging phenotypes in Atrx …

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 neurons of …

De-Coding The Impact Of Evolved Changes In Gene Expression And Cellular Phenotype On Primate Evolution, Trisha Zintel

Doctoral Dissertations

The goal of the dissertation work outlined here was to investigate the influence of proximal processes contributing to evolutionary differences in phenotypes among primate species. There are numerous previous comparative analyses of gene expression between primate brain regions. However, primate brain tissue samples are relatively rare, and my results have contributed to the pre-existing data on more well-studied primates (i.e. humans, chimpanzees, macaques, marmosets) as well as produced information on more rarely-studied primates (i.e. patas monkey, siamang, spider monkey). Additionally, the primary visual cortex has not previously been as extensively studied at the level of gene expression as other brain …

Cis-Regulatory Analysis Of Onecut1 Expression In Fate-Restricted Retinal Progenitor Cells, Sruti Patoori, Nathalie Jean-Charles, Ariana Gopal, Sacha Sulaiman, Sneha Gopal, Brian Wang, Benjamin Souferi, Mark Emerson

Publications and Research

Background: The vertebrate retina consists of six major classes of neuronal cells. During development, these cells are generated from a pool of multipotent retinal progenitor cells (RPCs) that express the gene Vsx2. Fate-restricted RPCs have recently been identified, with limited mitotic potential and cell fate possibilities compared to multipotent RPCs. One population of fate-restricted RPCs, marked by activity of the regulatory element ThrbCRM1, gives rise to both cone photoreceptors and horizontal cells. These cells do not express Vsx2, but co-express the transcription factors (TFs) Onecut1 and Otx2, which bind to ThrbCRM1. The components of the gene regulatory networks that control …

Neurodegenerative Modeling: Tau Protein, Degradative Pathways, And Gene Expression Profiling Of Human Ipsc-Derived Neural Precursors And Differentiated 3-D Neural Sphere Versus 2-D Monolayer Cultures, Kyle H. Anthoney

Cal Poly Humboldt theses and projects

Human induced pluripotent stem cells offer a model for human brain development and disease by differentiation into brain organoids; however, current neural culture systems lack the microenvironment, neuronal circuits and connectivity, vascular circulation, and immune system that exist in vivo. After differentiation and development of neuronal and non-neuronal cell types within two formats of cell cultures, we can visualize and recapitulate in vivo protein accumulation, gene expression, and degradative processes such as autophagy. Using RNA extraction, purification methods and reverse transcription I compared traditional monolayer cultures and novel 3-D neural sphere cultures via gene expression analysis. This analysis indicated …

Characterizing The Requirements For The Matricellular Protein, Dccn, In Nervous System Function, Elizabeth L. Catudio Garrett

Graduate Student Theses, Dissertations, & Professional Papers

The brain is organized as a complex network of specialized neurons that communicate via a combination of electrical and chemical signals. Our brains function to generate movement, control organ function, or direct complex behaviors; all of which requires the ability to regulate the flow of communication between circuits and networks. Work in this thesis addresses two areas of neuron communication: first, how does the release of more than one neurotransmitter from a single neuron impact behavior, and second, are matricellular proteins (MCPs) key contributors to synaptic transmission and neuron function? The conserved CCN family of MCPs have a …

Non-Invasive Method For Leptin Supplementation In Zebrafish (Danio Rerio), Regan Mcnamara

Williams Honors College, Honors Research Projects

I tested the hypothesis that recombinant leptin protein can be introduced to zebrafish in vivo through non-invasive soaking in a solution containing the protein. One way to study various molecules’ effects in vivo is through intraperitoneal or intracerebroventricular injections during the embryonic or larval stage, which is invasive, difficult to administer, and can have a high mortality rate. 48 hours post fertilization (hpf) zebrafish were soaked in a His-tagged recombinant leptin protein solution at 10 nM and 100 nM concentrations (produced by Genscript). After soaking, zebrafish larvae were washed extensively to remove all recombinant protein on their exterior before homogenization. …

Reprograming Neuronal Cells By Overexpression Of Fibroblast-Specific Transcription Factors, Abdulmohsen Alanazi

Masters Theses

In mammals, a complex system of regulatory signals distinguishes tissues, structures and functions. Combinations of transcription factors and co-factors regulate activation and repression of genes that result in cellular differentiation. Whole genome arrays allow the monitoring of genomic expression in specific tissues. Fibroblast microarray studies have shown candidate genes that may be involved in fibroblast identification, including genes that express transcription factors Prrx1, Snai2 and Twist1. A previous study showed that the Prrx1 and Snai2 could reactivate a fibroblast phenotype in hybrid cells that had lost fibroblast identity. Furthermore, overexpression of these factors in liver-derived cells strongly repressed liver gene …

Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani

Theses and Dissertations--Pharmacy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.

The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …

Tfap2e/Ap-2e Is A Transcriptional Regulator Controlling Neuronal Identity And Circuitry Formation In The Mouse Accessory Olfactory System, Jennifer M. Lin

Legacy Theses & Dissertations (2009 - 2024)

Developmental progression is driven by specific spatiotemporal gene expression, which give rise to consistently patterned organisms despite environmental and genetic variation. The specific activation of robust gene regulatory networks that define tissue structure and individual cellular identity are necessary for tissue and cell specific programs to be activated. Cellular specification is guided by the interplay of intrinsic and extrinsic signals at specific developmental timepoints. The molecular mechanisms underlying the acquisition and maintenance of individual cellular identity remains a fundamental question across biological systems. Understanding the regulatory networks controlling the acquisition of neuronal identity, diversity, and connectivity in the formation of …

Role Of Smad4 Dependent Signaling In Controlling The Functioning And Connectivity Of Basal Vomeronasal Sensory Neurons, Ankana S. Naik

Legacy Theses & Dissertations (2009 - 2024)

ABSTRACT