Molecular and Cellular Neuroscience Commons^™

Cerebro-Vascular Disruption Mediated Initiation And Propagation Of Traumatic Brain Injury In A Fluid Percussion Injury Model, Xiaotang Ma

Dissertations

Traumatic brain injury (TBI) is a major health problem for over 3.17 million people in the US. There is no FDA-approved drug for the treatment because the injury mechanisms have not been clearly identified. The knowledge gap is addressed here by the lateral fluid percussion injury (FPI) rat model, through the understanding of layer-structured mechanisms from physical vascular rupture to acute necrosis, as well as biochemical changes in perivascular space as secondary events.

Firstly, the cerebrovascular hemorrhage and related infarct volume are investigated as the primary events in moderate FPI, which is found to be increased with injury severity in …

Towards A Unified Disease Mechanism For Trna Synthetase-Mediated Peripheral Neuropathy, Emily L. Spaulding

Electronic Theses and Dissertations

Charcot-Marie-Tooth disease (CMT) is a debilitating inherited peripheral neuropathy resulting in progressive distal muscle atrophy and loss of sensation. CMT is genetically heterogeneous, with mutations in over 80 different genes leading to demyelinating or axonal forms. There are genetically similar subgroups, including the largest protein family implicated in the disease, the tRNA synthetases (ARSs). ARSs are responsible for aminoacylation of tRNAs during translation and are therefore ubiquitously expressed and essential proteins. Dominant mutations in at least five ARSs cause axonal forms of CMT. How mutations in ARSs cause CMT is unclear, however, the similar clinical presentation of patients suggests shared …

Nanomedicine-Driven Neuropathic Pain Relief In Rat Model Is Associated With Macrophage Polarity And Mast Cell Activation, Muzamil Saleem

Electronic Theses and Dissertations

We explored the immune neuropathology underlying multi-day relief from neuropathic pain in a rat model initiated at the sciatic nerve by using a nanoemulsion-based nanomedicine as a biological probe. The nanomedicine is theranostic: both therapeutic (containing celecoxib drug) and diagnostic (containing near-infrared fluorescent (NIRF) dye) and is small enough to be phagocytosed by circulating monocytes. A model of neuropathic pain is initiated by tying four 1mm spaced knots around the sciatic nerve with chromic gut suture, which results in neuroinflammation, and a resultant pain-like behavior manifests. We show that pain-like behavior reaches a plateau of maximum hypersensitivity 8 days post-surgery, …

Roles Of Autism Gene Arid1b In Murine Brain Development And Behavior, Amanda L. Smith

Theses & Dissertations

Autism spectrum disorder (ASD) and intellectual disability (ID) are highly prevalent neurodevelopmental disorders characterized by social and communication deficits, stereotyped behaviors, cognitive dysfunction, and deficits in adaptive behaviors. The pathogenesis underlying these disorders remains unknown, and thus no pharmacologic or genetic therapies are currently available. Recent progress in the field has shown that haploinsufficiency of the AT-rich interactive domain-containing 1B (ARID1B) gene is a genetic cause of ASD and ID. Our lab recently developed an Arid1b knockout mouse model to better study its role in the pathogenesis of these disorders. One theory regarding the cause of neurodevelopmental disorders …

Cholesterol Biosynthesis In The Nervous System With An Emphasis On Desmosterolosis, Luke Allen

Theses & Dissertations

Cholesterol biosynthesis is integral to proper neurodevelopment due to the reliance on de novo synthesis of cholesterol in the brain. Disruptions in this process have devastating outcomes for human life characterized by several phenotypic manifestations concomitant with developmental delay. The cholesterol biosynthesis disorder desmosterolosis is an extremely rare disorder with a severe clinical phenotype, however, the models used to study this disease are not well characterized. In addition to genetic disruptions in cholesterol biosynthesis, pharmacological perturbation is an understudied side effect of many commonly prescribed drugs. Here we present a characterization of the sterol profile of the mouse model of …

Role Of Astrocyte-Derived Extracellular Vesicles In Neuroinflammation Mediated By Drug Abuse, Ke Liao

Theses & Dissertations

Neuronal damage and neuroinflammation is a hallmark feature of HIV-associated neurological disorders (HANDs). Opioids abuse accelerates the incidence and progression of HAND; however, the mechanisms underlying the potentiation of neuropathogenesis by these drugs remain elusive. Extracellular vesicles (EVs) are essential conduits in HIV and drug abuse-mediated synaptodendritic injury and neuroinflammation. Findings from our group have demonstrated that astrocyte-derived EV (ADEV)-miRNA-29b mediates HIV Tat and morphine-induced neuronal injury, thus underscoring the importance of such interactions in NeuroHIV.

Besides, HIV Tat and morphine-mediated synaptodendritic injury via ADEVs, we are also interested in whether ADEVs contributes to neuroinflammation. Microglia are critical players in …

Assessing The Morphology Of Vesicles In Inhibitory Symmetric Synapses In Safety And Fear Conditions In The Rat Lateral Amygdala, Valerie Kress

Honors Scholar Theses

There is a significant lack of research on vesicle morphology in inhibitory synapses in the rat lateral amygdala. Published research focuses heavily on excitatory synapses in different parts of the rat brain and even this research rarely focuses on the different vesicle types in axons. It is reported that in these axons, synaptic vesicles traditionally contain neurotransmitters while small dense core vesicles contain active zone proteins and large dense core vesicles contain neuropeptides. This study aims to find correlations between vesicle morphology, location, contents, and potential function of each of the different types of vesicle in inhibitory axons.

After reviewing …

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms are partially …

Understanding Object Motion Encoding In The Mammalian Retina., Victor Julian Depiero

Electronic Theses and Dissertations

Phototransduction, transmission of visual information down the optic nerve incurs delays on the order of 50 – 100ms. This implies that the neuronal representation of a moving object should lag behind the object’s actual position. However, studies have demonstrated that the visual system compensates for neuronal delays using a predictive mechanism called phase advancing, which shifts the population response toward the leading edge of a moving object’s retinal image. To understand how this compensation is achieved in the retina, I investigated cellular and synaptic mechanisms that drive phase advancing. I used three approaches, each testing phase advancing at a …

A Novel Switch-Like Function Of Delta-Catenin In Dendrite Development, Ryan Baumert

Dissertations & Theses (Open Access)

The formation of neuronal networks in the brain is tightly regulated, and dependent on the morphology of dendrites, the branch-like signal-receiving structures extending from neurons. Disruptions in dendrite development, or dendritogenesis, can lead to the atypical neuronal connectivity associated with multiple neurodevelopmental diseases. My research addresses molecular processes that underlie dendritogenesis via analysis of a pair of novel interactions involving the protein delta-catenin.

In neurons, delta-catenin localizes to dendrites and synapses, where it functions in their development and maintenance. Structurally, delta-catenin possesses a central Armadillo domain and a C-terminal PDZ-binding motif. This motif associates with PDZ domain-containing proteins, and is …

Investigating The Effects Of Excitotoxic Stimuli On The Suprachiasmatic Nucleus, Rachel A. Brandes

Chancellor’s Honors Program Projects

No abstract provided.

Modeled Microgravity Induces Neutrophil Extracellular Trap (Net)Osis Formation And Reduced Phagocytosis Of Polymorphonuclear Neutrophils, Amber M. Paul

Publications

Spaceflight can dysregulate immunity, by way of increasing granulocytes numbers with impaired function. Polymorphonuclear neutrophils (PMN) are granulocytes that are first responders to infection or injury, and consist of the largest pool of immune cells in humans. PMNs function during innate immunity, through phagocytosis and promotion of inflammation, via the release of reactive oxygen species (ROS) mediators and granule-containing enzymes, such as myeloperoxidase (MPO) and NADPH oxidase-2 (NOX-2). In addition, neutrophil extracellular trap (NET) formation is another mechanism of PMN surveillance that works independently of engulfment phagocytosis, and is a last resort function that can induce NETosis or PMN-specific cell …

Altered Proteasome Expression And Nuclear Factor (Erythroid-Derived 2)-Like Signaling In Experimental Autoimmune Encephalomyelitis, Kara L. Shanley

Biomedical Sciences ETDs

Multiple sclerosis (MS) is a complex neurological disorder characterized by the interactions between heightened inflammation, oxidative stress and neurodegeneration. We and others have previously demonstrated that proteasome dysfunction and its consequences are also important factors in the pathology of both MS and its rodent model, experimental autoimmune encephalomyelitis (EAE). While proteasome subunit alterations in EAE have been observed, the underlying mechanisms are poorly understood. The first goal of this dissertation was to characterize the mechanisms that regulate proteasome expression and composition in neural cells in EAE and in vitro.

Immunohistochemical analysis of the EAE spinal cord shows changes in …

Sex Specific Electrophysiology Of Aromatase Neurons In The Medial Amygdala, Marcelo Henrique Correia

Masters Theses

The medial amygdala (MeA) is a central node in the interwoven circuits that regulate social behavior based on pheromones. Aromatase-expressing (arom⁺) neurons in the MeA are key for the establishment and maintenance of sex differences. Here, we characterized the intrinsic electrophysiological properties of arom⁺ neurons and non-aromatase (arom^-) neurons in the MeA of male and female mice. Most electrophysiological properties were similar for arom⁺ neurons in the MeA between sexes, but the relative refractory period was twice as large in female mice. We also show that the firing pattern and firing frequency is markedly …

Lysosomes Mediate Rab27b-Dependent Secretion Of Beta-Amyloid, Shany Lahan

Electronic Thesis and Dissertation Repository

Extracellular deposition of beta-Amyloid (Aβ) is an early event in Alzheimer’s disease development. However, it is not known how Aβ is secreted. Lysosomes readily undergo calcium-dependent exocytosis, a process that relies on small GTPase Rab27b. In addition, lysosomal enzymes have been found within extracellular amyloid plaques. We hypothesized that lysosomes mediate Rab27b-dependent exocytosis of Aβ. Neuro-2a cells were transfected with wild-type or mutant Rab27b constructs and/or a lysosomal marker. Cells were incubated with Aβ monomers and imaged using a confocal microscope before and after stimulation of calcium-dependent exocytosis. We observed a significant decrease in lysosome and Aβ co-localization post-treatment in …

Micrornas Are Necessary For Bmp-7-Induced Dendritic Growth In Cultured Rat Sympathetic Neurons, Vidya Chandrasekaran

Vidya Chandrasekaran

Development And Sensory Experience Dependent Regulation Of Microglia In Barrel Cortex, Joshua C. Brumberg, John Kalambogias, Chia-Chien Chen, Safraz Khan, Titus Son, Carolyn Headlam, Cindy Lin

Publications and Research

The barrel cortex is within the primary somatosensory cortex of the rodent, and processes signals from the vibrissae. Much focus has been devoted to the function of neurons, more recently, the role of glial cells in the processing of sensory input has gained increasing interest. Microglia are the principal immune cells of the nervous system that survey and regulate the cellular constituents of the dynamic nervous system. We investigated the normal and disrupted development of microglia in barrel cortex by chronically depriving sensory signals via whisker trimming for the animals’ first postnatal month. Using immunohistochemistry to label microglia, we performed …

Hyaluronan At The Brain-Environment Interface, Donald M. Thevalingam

Dissertations, Theses, and Capstone Projects

Hyaluronan (HA; Hyaluronic Acid), a primary scaffolding component of the brain extracellular matrix, serves as an integral structural component to the brain extracellular space (ECS). The fossorial African naked mole-rat (Heterocephalus glaber; NM-R), a mammal which lives in a low-oxygen environment and is capable of tolerating hypoxia and hypercapnia, has been shown to synthesize and sustain a unique high-molecular-mass variant of hyaluronan macromolecule (HMM-HA). This body of work highlights HA’s role in mediating the interplay between brain ECM composition, ECS structure, and cell viability.

Here we employ the NM-R as a unique animal model to observe the role of the …

Distributions Of Hypothalamic Neuron Populations Co-Expressing Tyrosine Hydroxylase And The Vesicular Gaba Transporter In The Mouse., Kenichiro Negishi, Mikayla A. Payant, Kayla S. Schumacker, Gabor Wittman, Rebecca M. Butler, Ronald M. Lechan, Harry W. M. Steinbusch M, Arshad M. Khan, Melissa J. Chee

Arshad M. Khan, Ph.D.

No abstract provided.

Assessing The Role Of Drosophila Melanogaster Neuroligin 3 On Social Spacing And Climbing Behaviour, J. Wesley Robinson

Electronic Thesis and Dissertation Repository

Autism spectrum disorders can be clinically defined in part by impairments of social interactions. Social interactions can be modeled in Drosophila melanogaster with behaviours such as social spacing. Here, I examined the effects of autism-related gene neuroligin 3 on fly social spacing. I hypothesized if neuroligin 3 is mutated or gene expression is targeted for knockdown, then flies will have altered social space in males and females at different ages. Using the social space assay, I found that different mutations to neuroligin 3 change the fly’s behavior, in a mutation and sex-specific manner. Using an antibody against Nlg3, I localized …

Mice Exposed To Combined Chronic Low-Dose Irradiation And Modeled Microgravity Develop Long-Term Neurological Sequelae, Amber M. Paul, Eliah G. Overbey, William A. Da Silveira, Candice G.T. Tahimic, Sigrid S. Reinsch, Nathaniel Szewczyk, Seta Stanbouly, Charles Wang, Jonathan M. Galazka, Xiao Wen Mao

Publications

Spaceflight poses many challenges for humans. Ground-based analogs typically focus on single parameters of spaceflight and their associated acute effects. This study assesses the long-term transcriptional effects following single and combination spaceflight analog conditions using the mouse model: simulated microgravity via hindlimb unloading (HLU) and/or low-dose γ-ray irradiation (LDR) for 21 days, followed by 4 months of readaptation. Changes in gene expression and epigenetic modifications in brain samples during readaptation were analyzed by whole transcriptome shotgun sequencing (RNA-seq) and reduced representation bisulfite sequencing (RRBS). The results showed minimal gene expression and cytosine methylation alterations at 4 months readaptation within single …

Development Of An Imaging Analysis Algorithm For Fluorescence-Based High Content Screening In Parkinson’S Disease, Ryan Arlinghaus

The Journal of Purdue Undergraduate Research

No abstract provided.

The Functional Conservation Of Frazzled In Insects, Benjamin Wadsworth

Graduate Theses and Dissertations

Axons in the developing embryo receive and react to signals that direct their growth to reach target tissues at specified locations. The signal pathways that direct midline crossing of axons during embryonic development have been comprehensively examined in the past years using the Drosophila ventral nerve cord or the spinal cord as a model system. A number of these signaling mechanisms are conserved, however disparities have been found between species in general strategy or the molecular signals controlling the response of axons to guidance cues.

The Netrin-Frazzled pathway has been shown to aid in midline crossing of axons in the …

The Functional And Structural Analysis Of Drosophila Robo2 In Axon Guidance, Lafreda Janae Howard

Graduate Theses and Dissertations

In animals with complex nervous systems such as mammals and insects, signaling pathways are responsible for guiding axons to their appropriate synaptic targets. Importantly, when this process is not successful during the development of an organism, outcomes include catastrophes such as human neurological diseases and disorders. It is vital to determine the underlying causes of such diseases by understanding the development of the nervous system. There are many pathways that have been identified to play a role in this, however, we lack an understanding of how these pathways can promote such diverse outcomes in different populations of neurons. These pathways …

Brain-Specific And Systemic Inflammatory Response Following Repetitive Concussive Impact In A Mouse Model, So Young Eo

Electronic Thesis and Dissertation Repository

Concussion is the most common form of mild traumatic brain injury (mTBI). TBI resolution is modulated by neuroinflammation, which is augmented by the infiltration of innate immune cells from the circulation. Peripheral, myeloid immune cells not only invade neural tissues but other organs as well causing local inflammation and tissue damage, known as systemic inflammatory response syndrome. Here, I assessed the temporal and anatomical nature of the neural and systemic cellular inflammatory response to repetitive, mTBI in a 3-hit mouse model of concussion. The results showed significant microglial activity, accumulation of peripheral myeloid cells and prominent axonal damage post-injury. The …

Comparison Of Nickel And Cobalt Induced Hypoxic Cell Models Using Cell Proliferation Assay, Melissa Delcasale

Seton Hall University Dissertations and Theses (ETDs)

Hypoxia is an imbalance in oxygen delivery and oxygen consumption, ultimately affecting cell survival. Low levels of oxygen diminish adenosine triphosphate synthesis resulting from a decline in oxidative phosphorylation in the mitochondria, therefore inducing apoptosis and cell death. To create a hypoxia mimicked environment, we used hypoxia mimetic compounds cobalt and nickel to treat human neuroblastoma (NMB) cells. Using hypoxic mimic human neuronal cell models, we examined and compared the effects of compound-induced hypoxia on NMB cell proliferation. The cells were treated with 100mM and 300mM concentrations of each compound at 24- and 48-hour intervals. To investigate cell proliferation, the …

Molecular Specialization Of Gabaergic Synapses On The Soma And Axon In Cortical And Hippocampal Circuit Function And Dysfunction, April Contreras, Dustin J. Hines, Rochelle M. Hines

Psychology Faculty Research

The diversity of inhibitory interneurons allows for the coordination and modulation of excitatory principal cell firing. Interneurons that release GABA (γ-aminobutyric acid) onto the soma and axon exert powerful control by virtue of proximity to the site of action potential generation at the axon initial segment (AIS). Here, we review and examine the cellular and molecular regulation of soma and axon targeting GABAergic synapses in the cortex and hippocampus. We also describe their role in controlling network activity in normal and pathological states. Recent studies have demonstrated a specific role for postsynaptic dystroglycan in the formation and maintenance of cholecystokinin …

Psychological Stress Modulates Synaptic Mechanisms For Prostaglandin E2-Mediated Hpa Axis Activation, Meagan Wiederman

Electronic Thesis and Dissertation Repository

Immune-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis elevates glucocorticoids, anti-inflammatory hormones, promoting the effective resolution of inflammation. Psychological stress can modulate this anti-inflammatory mechanism, but the mechanisms underlying this modulation remain largely unknown. The immune-induced HPA axis activation is, in large part, mediated by prostaglandin E₂ (PGE₂), an inflammatory mediator. In the brain, PGE₂ attenuates GABAergic synaptic transmission onto corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN) that act as the apex of the HPA axis. The removal of GABA-mediated inhibition (i.e. disinhibition) excites CRH neurons and, consequently, activates the HPA axis. …

Evolutionary Expansions And Neofunctionalization Of Ionotropic Glutamate Receptors In Cnidaria, Ellen G. Dow

FIU Electronic Theses and Dissertations

Reef ecosystems are composed of a variety of organisms, transient species of fish and invertebrates, microscopic bacteria and viruses, and structural organisms that build the living foundation, coral. Sessile cnidarians, corals and anemones, interpret dynamic environments of organisms and abiotic factors through a molecular interface. Recognition of foreign molecules occurs through innate immunity via receptors identifying conserved molecular patterns. Similarly, chemosensory receptors monitor the environment through specific ligands. Chemosensory receptors include ionotropic glutamate receptors (iGluRs), transmembrane ion channels involved in chemical sensing and neural signal transduction. Recently, an iGluR homolog was implicated in cnidarian immunological resistance to recurrent infections of …

Investigation Of Even-Skipped, A Developmentally-Regulated Gene Controlling Neural Segmentation In Dragonflies, Kathryn Bangser

Honors Theses

A comprehensive understanding of the genetic mechanisms underlying pattern formation and neurogenesis is necessary in order to trace the evolutionary history of insect embryogenesis.

One of the most important processes of embryogenesis is the organized pattern formation that allows for proper body segmentation and neural development. Proper segmentation, which relies on a series of specific gene expressions, is necessary for the development of an operational nervous system. Even-skipped (eve), one such regulatory gene, has been studied extensively in certain model organisms, and theories regarding the evolution of its functional role could be further elucidated by visualizing its expression …