Nervous System Diseases Commons^™

The Role Of Micrornas In The Pathophysiology Of Neonatal Hypoxic-Ischemic Brain Injury, Eric S. Peeples

Theses & Dissertations

Neonatal hypoxic-ischemic brain injury (HIBI) is a devastating injury resulting from impaired blood flow and oxygen delivery to the brain at or around the time of birth. The subsequent metabolic failure and cellular injury in the brain can be partially attenuated by rapid initiation of therapeutic hypothermia, but even with prompt induction of hypothermia, more than one in four survivors suffer from major developmental disabilities – an indication of the critical need for more effective therapies. MicroRNAs (miRNA) may be able to act as therapeutic targets in neonatal HIBI; however, very little is known about the endogenous expression of miRNAs …

Characterization Of Novel Animal Models For Parkinson’S Disease, Mohannad Almikhlafi

Theses & Dissertations

Parkinson’s disease (PD) is neurodegenerative disorder characterized by dopaminergic neuronal loss in the substantia nigra (SN) pars compacta. Mutations in DJ-1, PINK1 and Parkin lead to PD in humans; however, in mice, mutations or knockout of these genes do not lead to disease. Development of small animal models mimicking PD pathogenesis would enable better understanding of the disease. Here, we examined two approaches using laboratory rats. First, DJ-1 knockout rats have been reported to develop movement disorders and loss of neurons similar to human PD. Comprehensive analysis of mitochondrial proteomic alteration in isolated synaptic mitochondria from DJ-1 knockout rats using …

Electrophysiological Biomarkers Of Chemotherapy-Related Cognitive Impairment In Hematological Malignancy Patients, David E. Anderson

Theses & Dissertations

Multiple cancer populations frequently report cognitive impairment following treatment with chemotherapy agents (“chemo-brain”). Impaired neuropsychological performance is commonly reported in cognitive domains of attention and executive function. Understanding neural mechanisms underlying cognitive impairments is essential to developing prevention and rehabilitation strategies. Brain imaging studies frequently show chemotherapy-related impairments within the attentional control network, which is comprised of a constellation of cortical regions that govern reportedly impaired cognitive functions. In the current dissertation research, I developed a novel electrophysiology battery aimed at recording near-instantaneous neural activity within the attentional control network during cognitive task performance. Cancer patients diagnosed with hematological malignancy …

Evaluation Of Immune-Modulating Therapies For Parkinson's Disease, Katherine E. Olson

Theses & Dissertations

Parkinson’s disease (PD) is the second most common neurodegenerative

disorder, second only to Alzheimer’s disease (AD). It is characterized by a

progressive loss of dopaminergic neurons along the nigrostriatal axis and the

formation of proteinaceous inclusions of alpha-synuclein (α-syn). Secondary to

the loss of dopaminergic neurons is a progression in motor and non-motor

symptoms. Motor symptoms are characterized by slowness in movement,

stiffness and tremor. Non-motor symptoms include depression, constipation,

sleep abnormalities and loss of sense of smell. The cause of disease remains

incompletely understood. However, age, genetics, environment, viral infection,

and interplay between the innate and adaptive immune system …

Novel Therapeutic Approaches For Juvenile Neuronal Ceroid Lipofuscinosis (Cln3), Megan Elizabeth Bosch

Theses & Dissertations

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a lysosomal storage disease caused by autosomal recessive mutations in CLN3. Neuronal loss is thought to occur via glutamate excitotoxicity; however, little is known about neuron-astrocyte glutamate regulation in JNCL. We discovered that Cln3^Δex7/8 astrocytes have significantly lower basal spontaneous Ca²⁺ oscillations and decreased responses to glutamate, indicating a disrupted signaling network. Cln3^Δex7/8 astrocytes also displayed significantly lower basal mitochondrial respiration and ATP production, suggesting impaired metabolic functions. Concurrent with diminished astrocyte metabolism and Ca²⁺ signaling, Cln3^Δex7/8 neurons were hyper-responsive to glutamate stimulation. These studies suggest that CLN3 …

The Role Of Glutaminase And Extracellular Vesicles In Macrophages And Microglia, Beiqing Wu

Theses & Dissertations

Glutamate serves as a crucial excitatory neurotransmitter that is essential for the proper functioning of the brain. However, excess levels of glutamate are neurotoxic and contribute to the pathogenesis of various neurodegenerative diseases, inducing HIV-1 associated neurocognitive disorders (HAND). Glutaminase 1 (GLS1) is an important mitochondrial enzyme responsible for producing glutamate from glutamine. GLS1 is upregulated during HAND and released from mitochondria to cytosol and extracellular space. However, why and how GLS1 is released remains unknown. In chapter II, we demonstrated that extracellular vesicles (EVs) carry GLS1 as cargos from cytosol to extracellular space during HIV infection and innate immune …

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 …

The Feedforward And Feedback Controls On Gait In Adults With Diabetes, Chun-Kai Huang

Theses & Dissertations

There are nearly 26 million people with diabetes mellitus (DM) in the US, and half of chronic DMs develop somatosensory deficits due to diabetic polyneuropathy or diabetic peripheral neuropathy (DPN). The absence or impaired somatosensory feedback (e.g. touch sensation or joint proprioception) resulted from the damage of large nerve fiber, and motor deficits such as attenuated muscle strength and abnormal plantar pressure of lower extremity have been identified in DPN, and these sensorimotor impairments lead to an increased number of falls. To reduce the risk of falling, a well-coordinated and adapted limb movement driven by the feedforward (anticipatory) and feedback …

Stress Experienced By Respite Care Workers And Family Caregivers When Caring For Alzheimer's Patients, Monica D. Minewiser

Theses & Dissertations

Changing demographics and cost containment in health care in caring for the Alzheimer's Disease (AD) patient has given birth to a growing need for respite care workers. The purpose of the study was to determine whether the stress level of a respite care worker who works with an AD patient in a noninstitutionalized setting on a daily basis will be significantly less than that of a family caregiver when caring for an AD patient. The Revised Memory and Behavior Problem Checklist (RMBPC) was the instrument used to measure stress. This is a questionnaire consisting of 24 questions and allows 5 …