Neuroscience and Neurobiology Commons^™

Target Validation And Pharmacological Characterization Of Novel Nmdar Modulators, Kiran Sapkota

Theses & Dissertations

The N-methyl-D aspartate receptors (NMDARs) are ligand-gated ion channels, which play important roles in learning and memory. Excessive activity of NMDARs is implicated in damage due to stroke and neurodegenerative diseases, whereas hypoactivity of NMDARs contributes to schizophrenia. The initial goal of my dissertation is to evaluate the potential role of the GluN2D-containing NMDARs in neuropathological, behavioral and cognitive alterations associated with schizophrenia and characterize the pharmacology and mechanisms of action of NMDAR modulators which could potentially be used to modulate these receptors in schizophrenia.

A subanesthetic dose of the NMDAR antagonist ketamine elicits symptoms of schizophrenia. This property led …

Mitogen And Morphogen Signaling Dysregulation: Pathophysiological Influence In Pancreatic Cancer And Alzheimer’S Disease, Eric Cruz

Theses & Dissertations

Although the etiology of a particular disease will vary, there are genetic and epigenetic bottlenecks that frequently converge resulting in dysregulation of mitogenic and morphogenetic signaling. This propensity is acutely experienced in malignancy and neurodegenerative disease.

Here, we have first investigated the role of dysregulated signaling in the context of pancreatic cancer (PC). Morphogenetic signaling has been regarded as a pleiotropic pathway with the potential to promote and inhibit metastatic features. Our investigation of bone morphogenetic protein 2 (BMP-2), an archetypical member of the BMP superfamily, has revealed the presence of extracellular, intracellular, and long non-coding RNA products. Our findings …

Motor Control In Individuals With Multiple Sclerosis, David Arpin

Theses & Dissertations

This dissertation explored motor control in individuals with multiple sclerosis (MS) by quantifying the behavioral and neurophysiological deficits present in these individuals. We behaviorally quantified the precision of the ankle plantarflexor musculature of individuals with MS. Our results indicated that the individuals with MS had a greater amount of variability in the precision of the isometric ankle torques, and that this greater variability was related to decreased walking performance. To further explore whether these motor control deficits were due to aberrant cortical activity associated with planning motor actions, we used magnetoencephalography to assess the motor planning and execution stages of …

Global Gene Expression Profiling Of Healthy Human Brain And Its Application In Studying Neurological Disorders, Simarjeet K. Negi

Theses & Dissertations

The human brain is the most complex structure known to mankind and one of the greatest challenges in modern biology is to understand how it is built and organized. The power of the brain arises from its variety of cells and structures, and ultimately where and when different genes are switched on and off throughout the brain tissue. In other words, brain function depends on the precise regulation of gene expression in its sub-anatomical structures. But, our understanding of the complexity and dynamics of the transcriptome of the human brain is still incomplete. To fill in the need, we designed …

Voltage-Gated K+ Channels And Hiv-1-Induced Neural Injury: Implications For Pathogenesis Of Hiv-1-Associated Neurocognitive Disorders, Han Liu

Theses & Dissertations

Human immunodeficiency virus-1 (HIV-1)-associated neurocognitive disorder (HAND) is a subcortical disease involving neuronal loss and myelin damage. Myelin is deposited by oligodendrocytes through a complex process including oligodendrocyte progenitor cell (OPC) proliferation and maturation. Oligodendrocytes/OPCs are susceptible to viral proteins such as Tat and that myelin damage is associated with oligodendrocyte number decrease. It has been shown that activation of voltage-gated K⁺ (K_V) channels mediates apoptosis in various cell types. K_V1.3 is the most predominant K_V channel expressed in OPCs/oligodendrocytes and potentially involved in OPC developmental regulation. We studied the involvement of K_{V …}

Molecular Mechanisms Involved In Neurotoxicity Mediated By Hiv Proteins And Drug Abuse, Yu Cai

Theses & Dissertations

While the advancement of highly active antiretroviral therapy (HAART) has transformed the course of HIV/AIDS from a death sentence to a manageable chronic condition, the prevalence of a constellation of neurological disorders collectively termed as HIV-associated neurocognitive disorders (HAND) continues to persist in these patients. HAND is characterized by cognitive dysfunction, depression, impaired memory and/or deficits in motor skills. The underlying factors leading to HAND have been the subject of extensive research and are thought to be associated with HIV infection in the CNS combined with robust immune activation of resident cells of the CNS. In addition, there is a …

Expression And Function Of Inflammation-Associated Micrornas In Traumatic Brain Injury, Emily Harrison

Theses & Dissertations

MicroRNAs (miRNAs) are important regulators of gene expression. Many neurological diseases, including traumatic brain injury alter expression of miRNAs in the brain. However, the function of these molecules in the context of TBI is largely unknown. Here we report multiple potential roles for miRNAs in TBI, some of which extend beyond the traditional model of post-transcriptional regulation, highlighting that these RNA molecules may have broader implications for the neurobiology of disease. We found that miR-155 plays an essential role in interferon expression after CCI and that miR-155 contributes to TBI induced anxiety, potentially through regulation of interferons. Expression of miR-155 …