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Articles 31 - 56 of 56
Full-Text Articles in Neurosciences
Autotaxin In Central Nervous System Development And Disease, Natalie A. Wheeler
Autotaxin In Central Nervous System Development And Disease, Natalie A. Wheeler
Theses and Dissertations
During development, oligodendrocytes (OLGs), the myelinating cells of the central nervous system (CNS), undergo a stepwise progression during which OLG progenitors, specified from neural stem/progenitor cells, differentiate into fully mature myelinating OLGs. This progression along the OLG lineage is characterized by well-synchronized changes in morphology and gene expression patterns. The studies presented in this dissertation identified the extracellular factor Autotaxin (ATX) as a novel upstream signal modulating HDAC1/2 activity and gene expression in cells of the OLG lineage. Using the zebrafish as an in vivo model system, as well as rodent primary OLG cultures, this functional property of ATX was …
Post-Tbi Hippocampal Neurogenesis In Different Tbi Models, Kaushal S. Patel
Post-Tbi Hippocampal Neurogenesis In Different Tbi Models, Kaushal S. Patel
Theses and Dissertations
Traumatic brain injury (TBI) leads to short-term and long-term consequences that can cause many different life-long disorders. Studies of TBI have generally focused on the acute stage; however, it is now becoming important to investigate chronic responses following TBI as clinical reports of dementia and cognitive impairments have been linked to a history of TBI. Recent data have established that cognitive function is associated with hippocampal neurogenesis. Chronic injury induced changes in the brain may affect this endogenous process. Chronic responses following TBI include cell death pathways and inflammatory responses that are persistent in the brain for months to years …
Human Neural Progenitor Cells Are Productively Infected By R5-Tropic Hiv-1: Opiate Interactions On Infection And Function Involve Cdk5 Signaling, Joyce Magat Balinang
Human Neural Progenitor Cells Are Productively Infected By R5-Tropic Hiv-1: Opiate Interactions On Infection And Function Involve Cdk5 Signaling, Joyce Magat Balinang
Theses and Dissertations
Human immunodeficiency virus type 1 (HIV-1) is known to cause a spectrum of neurological, behavioral and motor deficits collectively termed as HIV-1 associated neurocognitive impairments (HAND). Opiates augment HIV-related CNS complications through both direct and indirect mechanisms that disrupt glial and neuronal function. All CNS macroglia and neurons derive from neural progenitor cells (NPCs) during development, and NPCs in the adult brain contribute to repair processes. Since disruptions in NPC function are known to impact CNS populations and brain function in a number of disease/injury conditions, we determined whether HIV ± opiate exposure affected the maturation and fate of human …
Mitochondrial Biogenesis And Electrical Properties Of Hpsc-Derived Motor Neurons, Laura O'Brien
Mitochondrial Biogenesis And Electrical Properties Of Hpsc-Derived Motor Neurons, Laura O'Brien
Theses and Dissertations
Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) hold great promise in the fields of drug development and regenerative medicine. If iPSCs reprogrammed from patient cells replicate what is seen in vivo they may be used as a model of disease. A process that is disrupted in many neurodegenerative diseases is mitochondrial biogenesis. One of these diseases is amyotrophic lateral sclerosis (ALS), which is characterized by loss of motor neurons in the brain and spinal cord. Differentiation of hPSCs into motor neurons offers a way to study a previous unavailable cell …
Axon Initial Segment Stability In Multiple Sclerosis, Suneel K. Thummala
Axon Initial Segment Stability In Multiple Sclerosis, Suneel K. Thummala
Theses and Dissertations
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by inflammation and demyelination. In addition to these hallmark features, MS also presents with axonal pathology, which is likely responsible for the signs and symptoms of the disease. Although prominent in MS, axonal pathology is frequently considered a consequence of demyelination and not a primary event. This conclusion is consistent with demyelination inducing the loss of specific axonal domains, known as the nodes of Ranvier that are responsible for the propagation of action potentials along the axon. In contrast, we propose that axonal pathology associated with MS …
Decreased Pain Severity And Differential Gene Expression Following Calmare Therapy, Jeffrey Petraco, Angela R. Starkweather, Amy Heineman
Decreased Pain Severity And Differential Gene Expression Following Calmare Therapy, Jeffrey Petraco, Angela R. Starkweather, Amy Heineman
UROP Posters
We present the results of a double-blinded randomized sham-controlled research study of a non-pharmacologic low back pain intervention. Calmare therapy is an neurocutanous electrical stimulation approach for pain management. The intervention group received Calmare therapy and the other received sham. Differences in pain severity and interference scores, pain sensitivity measures and gene expression profiles are reported. Patterns of downregulated gene expression suggest that Calmare may alter proteins involved in pain transduction may have implications for the treatment of other chronic pain conditions.
Effects Of Hiv-1 Viral Protein Tat On The Viability And Function Of Oligodendroglial Cells, Shiping Zou
Effects Of Hiv-1 Viral Protein Tat On The Viability And Function Of Oligodendroglial Cells, Shiping Zou
Theses and Dissertations
Myelin pallor is frequently reported in HIV patients, and can occur in the CNS prior to other evidence of disease process. Our exploratory studies showed that oligodendrocytes (OLs) are direct targets of HIV-1 Tat (transactivator of transcription). Tat induces a dose-dependent increase of intracellular Ca2+ level ([Ca2+]i) in cultured murine OLs, which can be attenuated by ionotropic glutamate receptor (iGluR) antagonists MK801 and CNQX. The Tat-induced [Ca2+]i increase leads to increased death in immature (O4+, MBP-), but not mature (O4+, MBP+) OLs, over 96 …
Meta-Analysis Of Gene Expression Studies, Umaporn Siangphoe
Meta-Analysis Of Gene Expression Studies, Umaporn Siangphoe
Theses and Dissertations
Combining effect sizes from individual studies using random-effects models are commonly applied in high-dimensional gene expression data. However, unknown study heterogeneity can arise from inconsistency of sample qualities and experimental conditions. High heterogeneity of effect sizes can reduce statistical power of the models. We proposed two new methods for random effects estimation and measurements for model variation and strength of the study heterogeneity. We then developed a statistical technique to test for significance of random effects and identify heterogeneous genes. We also proposed another meta-analytic approach that incorporates informative weights in the random effects meta-analysis models. We compared the proposed …
Psychoactive Synthetic Cathinones (Or 'Bath Salts'): Investigation Of Mechanisms Of Action, Farhana Sakloth
Psychoactive Synthetic Cathinones (Or 'Bath Salts'): Investigation Of Mechanisms Of Action, Farhana Sakloth
Theses and Dissertations
Synthetic cathinones represent threatening and high abuse-potential designer drugs. These are analogs of cathinone (the b-keto analog of amphetamine (AMPH)) a naturally occurring stimulant found in the plant Catha Edulis. Methcathinone (MCAT) was the first synthetic analog of cathinone to be identified in 1987 by Glennon and co-workers and it exerted its action primarily through the dopamine transporter (DAT). Most central stimulants exert their action via monomaine transporters by causing either the release (e.g. cathinone analogs such as MCAT) or by preventing the reuptake (e.g. cocaine) of the neurotransmitter dopamine (DA) thus increasing the extracellular synaptosomal concentration of this …
Effects Of Hiv-1 Tat On The Enteric Nervous, Joy Ngwainmbi
Effects Of Hiv-1 Tat On The Enteric Nervous, Joy Ngwainmbi
Theses and Dissertations
More than 1.2 million people are estimated to be currently living with the human immunodeficiency virus (HIV) in the United States of America. The gastrointestinal (GI) tract is both a major target and an important component of HIV pathogenesis. The GI processes that are dysregulated during HIV infection are controlled by the enteric nervous system (ENS). Indeed, both clinical and experimental studies have implicated the ENS in HIV and simian immunodeficiency virus (SIV) pathogenesis. In addition to direct viral effects, the HIV virus also indirectly affects the GI tract via cellular and/or viral toxins released by infected cells. Trans-activator of …
A Molecular Mechanism Regulating The Timing Of Corticogeniculate Innervation, Justin Brooks
A Molecular Mechanism Regulating The Timing Of Corticogeniculate Innervation, Justin Brooks
Theses and Dissertations
Visual system development requires the formation of precise circuitry in the dorsal lateral geniculate nucleus (dLGN) of the thalamus. Although much work has examined the molecular mechanisms by which retinal axons target and form synapses in dLGN, much less is known about the mechanisms that coordinate the formation of non-retinal inputs in dLGN. These non-retinal inputs represent ~90% of the terminals that form in dLGN. Interestingly, recently reports show that the targeting and formation of retinal and non-retinal inputs are temporally orchestrated. dLGN relay neurons are first innervated by retinal axons, and it is only after retinogeniculate synapses form that …
Osteopontin Expression During The Acute Immune Response Mediates Reactive Synaptogenesis And Adaptive Outcome, Julie Chan
Theses and Dissertations
Traumatic brain injury (TBI) is a worldwide epidemic as the number of victims living with the resulting cognitive and physical impairment continues to rise, principally due to limited treatment options which fail to address its multifaceted sequelae. By approaching TBI therapy from a molecular standpoint, we have the opportunity to develop a better understanding of the mechanisms which prevent effective recovery. With this information, we can move toward the identification of novel therapeutic treatments which target specific molecules to improve patient outcome following TBI. Here, we have focused on the therapeutic potential of osteopontin (OPN), an extracellular matrix (ECM) protein …
Thc-Mediated Induction Of Δfosb And Its Modulation Of Cb1r Signaling And Adaptation, Lazenka Matthew
Thc-Mediated Induction Of Δfosb And Its Modulation Of Cb1r Signaling And Adaptation, Lazenka Matthew
Theses and Dissertations
The main psychoactive and therapeutic effects of Δ9-tetrahydrocannabinol (THC) are mediated through cannabinoid type 1 receptors (CB1Rs). The therapeutic uses of THC are mitigated by the development of tolerance to these therapeutic effects, whereas tolerance does not readily develop to some of the side-effects of THC, like motor impairment and reward. The development of tolerance occurs through adaptations at CB1Rs, which include desensitization (G-protein uncoupling) and downregulation (receptor degradation). Brain region-dependent differences in THC-mediated adaptations are proposed to explain the differences in tolerance to various THC-mediated effects. These studies focused on whether ΔFosB, a stable transcription factor, could regulate CB1R …
Diffuse Traumatic Axonal Injury Within The Visual System: Implications For Visual Pathway Reorganization, Jiaqiong Wang
Diffuse Traumatic Axonal Injury Within The Visual System: Implications For Visual Pathway Reorganization, Jiaqiong Wang
Theses and Dissertations
Traumatic brain injury is a major health problem with much of its morbidity associated with traumatic axonal injury (TAI). To date, significant insight has been gained into the initiating pathogenesis of TAI. However, the specific anterograde and retrograde sequelae of TAI are poorly understood because the diffuse nature of TAI complicates data analysis. To overcome this limitation, we subjected transgenic mice expressing yellow fluorescent protein (YFP) within the visual system to central fluid percussion injury, and consistently generated diffuse TAI within the optic nerve that could easily be followed in the organized YFP positive fibers. We demonstrated progressive axonal swelling, …
Unique Features And Neuronal Properties In A Multisensory Cortex, W. Alex Foxworthy
Unique Features And Neuronal Properties In A Multisensory Cortex, W. Alex Foxworthy
Theses and Dissertations
UNIQUE FEAUTRES OF ORGANIZATION AND NEURONAL PROPERTIES IN A MULTISENSORY CORTEX Multisensory processing is a ubiquitous sensory effect that underlies a wide variety of behaviors, such as detection and orientation, as well as perceptual phenomena from speech comprehension to binding. Such multisensory perceptual effects are presumed to be based in cortex, especially within areas known to contain multisensory neurons. However, unlike their lower-level/primary sensory cortical counterparts, little is known about the connectional, functional and laminar organization of higher-level multisensory cortex. Therefore, to examine the fundamental features of neuronal processing and organization in the multisensory cortical area of the posterior parietal …
Overexpression Of Serum Response Factor In Astrocytes Improves Neuronal Plasticity In A Model Of Fetal Alcohol Spectrum Disorders, Arco P. Paul
Theses and Dissertations
Neuronal plasticity deficits underlie many of the neurobehavioral problems seen in Fetal Alcohol Spectrum Disorders (FASD). Recently, we showed that third trimester alcohol exposure lead to a persistent disruption in ocular dominance (OD) plasticity. For instance, few days of monocular deprivation results in a robust reduction of cortical regions responsive to the deprived eye in normal animals, but not in ferrets exposed early to alcohol. This plasticity deficit can be reversed if alcohol-exposed animals are treated with a phosphodiesterase type 1 (PDE1) inhibitor during the period of monocular deprivation. PDE1 inhibition can increase cAMP and cGMP levels, activating transcription factors …
The Role Of Calcineurin In Dendritic Remodeling And Epileptogenesis In A Rat Model Of Traumatic Brain Injury, John Campbell
The Role Of Calcineurin In Dendritic Remodeling And Epileptogenesis In A Rat Model Of Traumatic Brain Injury, John Campbell
Theses and Dissertations
Traumatic brain injury (TBI), a leading cause of death and disability in the United States, causes potentially preventable damage in part through the dysregulation of neural calcium levels. This dysregulation likely affects the activity of the calcium-sensitive phosphatase, calcineurin, with serious implications for neural function. To test this possibility, the present study characterized the role of calcineurin in a rat model of brain trauma, the lateral fluid percussion injury model. Golgi-Cox histochemistry revealed an acute post-TBI loss and delayed overgrowth of dendritic spines on principal cortical cells. The spine loss appeared to require calcineurin activity, since administering a calcineurin inhibitor, …
Effects Of Early Alcohol Exposure On Ocular Dominance Plasticity, Crystal Lantz
Effects Of Early Alcohol Exposure On Ocular Dominance Plasticity, Crystal Lantz
Theses and Dissertations
Fetal alcohol spectrum disorder is the leading cause of mental retardation in the western world. It is associated with learning and sensory deficits. Some of these deficits are a result of faulty neuronal plasticity. Previously our lab has used ferrets to demonstrate that alcohol exposure during the third trimester of human gestation results in impaired ocular dominance plasticity (ODP). Here we have transferred this model to mice. Mice, treated with 5 mg/kg of ethanol on postnatal days 5, 7 and 9, exhibit a lack of ODP plasticity after 10 days of monocular deprivation (MD) during the critical period of visual …
Circuit Development In The Dorsal Lateral Geniculate Nucleus (Dlgn) Of The Mouse., Tania Seabrook
Circuit Development In The Dorsal Lateral Geniculate Nucleus (Dlgn) Of The Mouse., Tania Seabrook
Theses and Dissertations
The visual system is one of the most widely used and best understood sensory systems and the dorsal lateral geniculate nucleus (dLGN) of the mouse has emerged as a model for investigating the cellular and molecular mechanisms underlying the development and activity-dependent refinement of sensory connections. Thalamic organization is highly conserved throughout species and the dLGN of the mouse possesses many features common to higher mammals, such as carnivores and primates. Two general classes of neuron are present within the dLGN, thalamocortical relay cells and interneurons, both of which receive direct retinal input. Axons of relay cells exit dLGN and …
Cns Neural/Glial Progenitors As Targets Of Hiv-1 And Opiates: Effects On Proliferation And Population Dynamics May Alter Behavior Outcomes., Yun Kyung Hahn
Cns Neural/Glial Progenitors As Targets Of Hiv-1 And Opiates: Effects On Proliferation And Population Dynamics May Alter Behavior Outcomes., Yun Kyung Hahn
Theses and Dissertations
Human immunodeficiency virus (HIV) infected patients with a history of injection opiate abuse have higher incidences of acquired immunodeficiency syndrome (AIDS) and neurological dysfunction. The use of combined anti-retroviral therapy has significantly reduced the prevalence of mortality and progression to AIDS. Due to extended life expectancy, these patients are still at a great risk for HIV-associated neurological disorders and impairment in their later life. Neural progenitor cells (NPCs) play critical roles in brain growth and repair after injury and insult. Pediatric HIV patients whose glial populations are still developing are especially at risk for central nervous system (CNS) damage. Our …
Age Dependent Spatial Characteristics Of Epileptiform Activity In Malformed Cortex, L. Andrew Bell
Age Dependent Spatial Characteristics Of Epileptiform Activity In Malformed Cortex, L. Andrew Bell
Theses and Dissertations
Developmental cortical malformations are a major cause of intractable seizures. Determining the location and timing of susceptibility for epileptiform activity is critical to identifying what mechanisms contribute to epileptogenesis in any model. Using the freeze lesion rat model of polymicrogyria, we have identified, in lesioned cortex, these two aspects of epileptogenesis. Previous studies have demonstrated that epileptiform activity cannot be evoked prior to postnatal day (P) 12, but the malformed cortex is more susceptible to seizures as early as P10. An increase in excitatory afferents to the epileptogenic zone occurs before the onset of network epileptiform activity. Whether or not …
The Characterization Of The Anterograde And Retrograde Consequences Of Traumatic Axonal Injury In A Mouse Model Of Diffuse Brain Injury, John E. Greer
The Characterization Of The Anterograde And Retrograde Consequences Of Traumatic Axonal Injury In A Mouse Model Of Diffuse Brain Injury, John E. Greer
Theses and Dissertations
Traumatic axonal injury (TAI) is a consistent feature of (TBI) and is responsible for much of its associated morbidity. TAI is now recognized to result from progressive/secondary axonal injury, though much remains unknown in regards to the pathobiology and the long-term consequences of axonal injury. TAI has been described in the perisomatic domain, located within the neocortex following mild TBI, and within this domain has been linked to neuronal recovery, not neuronal cell death in the acute setting. Due to technical limitations, our understanding of the long-term fate of this neuronal population and the mechanisms responsible for permitting neuronal survival, …
Developmental Remodeling Of Relay Cells In The Dorsal Lateral Geniculate Nucleus (Dlgn) Of The Mouse And The Role Of Retinal Innervation, Rana El-Danaf
Theses and Dissertations
The dorsal lateral geniculate nucleus (dLGN) has become an important model for studying many aspects of visual system development. To date, studies have focused on the development of retinal projections and the role of activity in shaping the pattern of synaptic connections made with thalamocortical relay cells. By contrast, little is known about relay cells and the factors that regulate the growth and establishment of their dendritic architecture. In many systems, such growth seems consistent with the synaptotrophic hypothesis which states that synapse formation and dendritic growth work in a concerted fashion such that afferent input and the establishment of …
Characterization And Development Of A Stroke-Induced Model Of Acquired Epilepsy In Organotypic Hippocampal Slice Cultures: Role Of The Cannabinoid Cb1 Receptors In Modulation Of Neuronal Excitation And Inhibition, Julie Ziobro
Theses and Dissertations
Stroke is the most common cause of acquired epilepsy in persons 35 and older. The massive increase in extracellular glutamate during stroke causes a cascade of intracellular events that can lead to cell death or the molecular changes that initiate the development of epilepsy. In addition, many studies point to a modulatory role of the endocannabinoid system in controlling seizures. Animal models of stroke induced acquired epilepsy have been difficult to develop. Therefore, this dissertation was initiated to develop an organotypic hippocampal slice culture model of acquired epilepsy and examine the changes in distribution and function of the endogenous CB1 …
Autotaxin: A Regulator Of Oligodendrocyte Differentiation, Larra Yuelling
Autotaxin: A Regulator Of Oligodendrocyte Differentiation, Larra Yuelling
Theses and Dissertations
In order for oligodendrocyte progenitor cells (OPCs) to differentiate into fully mature, myelinating oligodendrocytes, they must be specified at the correct times and undergo coordinated changes in both gene expression and morphology. As oligodendrocytes differentiate, they transition from a bipolar morphology into a morphology characterized by a complex network of multiple processes, which will eventually generate membranous structures necessary for myelination of axonal segments. As changes are observed in cellular morphology, oligodendrocytes also undergo changes in their gene expression profile and express genes necessary for both early and later stages of development such as olig1 and myelin basic protein (mbp), …
The Role Of Synaptically Evoked Plateau Potentials In Retinogeniculate Development, Emily Dilger
The Role Of Synaptically Evoked Plateau Potentials In Retinogeniculate Development, Emily Dilger
Theses and Dissertations
We study the activity-dependent refinement of sensory systems by using the mouse retinogeniculate system as a model. Spontaneous retinal waves lead to robust excitatory post-synaptic activity in developing relay cells in the dorsal lateral geniculate nucleus (dLGN) of the thalamus and are reportedly needed to help guide the segregation of retinal inputs into eye-specific domains as well as for the pruning of extraneous retinal inputs onto single dLGN relay cells. The composition of retinally evoked post-synaptic activity activated by these retinal waves in dLGN is largely unknown, but based on our in vitro recordings, such activity seems well suited to …