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Articles 1 - 5 of 5
Full-Text Articles in Medical Neurobiology
Transcriptomic And Epigenomic Profiling Of Immune Cells Responses To Simian Immunodeficiency Virus Infection In The Brain, Xiaoke Xu
Theses & Dissertations
Human immunodeficiency virus type 1 (HIV-1) is an enveloped retrovirus that significantly impairs the human immune system. A common complication of HIV-1 infection is HIV-associated neurocognitive disorder (HAND), which, prior to the introduction of antiretroviral therapy (ART), led to considerable morbidity and mortality due to untreated neuropsychiatric manifestations. Although ART has substantially reduced the incidence of HIV-associated dementia (HAD), approximately 50% of people living with HIV (PLWH) continue to experience milder forms of HAND. The CNS is seeded by HIV during the acute phase of infection. Once in the brain, HIV targets and activates resident immune cells, primarily microglia and …
A Rare Delayed Neuropsychiatric Encephalopathy After Hyperbaric Oxygen Treatment For Carbon Monoxide Poisoning: A Couple’S Case Report, Sabrina Kasha, William J. Naber Ii, Michael Reimer
A Rare Delayed Neuropsychiatric Encephalopathy After Hyperbaric Oxygen Treatment For Carbon Monoxide Poisoning: A Couple’S Case Report, Sabrina Kasha, William J. Naber Ii, Michael Reimer
Graduate Medical Education Research Journal
Background: Carbon monoxide (CO) poisoning is caused when carbon monoxide builds up in the blood, most specifically due to its high binding affinity for the heme structure in hemoglobin. This can lead to serious tissue damage and even be fatal. CO poisoning is primarily the result of incomplete combustion of fuels, with common sources domestically and internationally including furnaces, gas heaters, generators, and motor vehicles.2 Symptoms tend to present as neuropsychiatric symptoms, such as dementia, psychosis, parkinsonism, and incontinence. There are few well-researched CO poisoning specific treatments, which suggest supplemental oxygen and hyperbaric oxygen are most effective. We present a …
Sequence-Specific Extracellular Micrornas Activate Tlr7, Niming Wu
Sequence-Specific Extracellular Micrornas Activate Tlr7, Niming Wu
Theses & Dissertations
Toll-like receptors (TLRs) play an important role in the innate immune system. Emerging evidence shows that TLRs, especially endosomal TLRs, can participate in CNS diseases by increasing the production of proinflammatory cytokines via recognition of microRNAs (miRNAs), however which of the miRNAs are able to activate signaling and whether specific sequence motifs are involved remains incompletely defined. Here we found that numerous miRNAs induced TNF-a production across multiple myeloid cell types, including microglia, and that this effect was abolished in cells deficient of TLR7. In particular, miR-20a-5p and miR-148b-3p preferentially stimulate cytokine secretion compared to miR-20b-5p and miR-148a-3p, respectively, despite …
Novel Therapeutic Approaches For Juvenile Neuronal Ceroid Lipofuscinosis (Cln3), Megan Elizabeth Bosch
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 Cln3Δex7/8 astrocytes have significantly lower basal spontaneous Ca2+ oscillations and decreased responses to glutamate, indicating a disrupted signaling network. Cln3Δex7/8 astrocytes also displayed significantly lower basal mitochondrial respiration and ATP production, suggesting impaired metabolic functions. Concurrent with diminished astrocyte metabolism and Ca2+ signaling, Cln3Δex7/8 neurons were hyper-responsive to glutamate stimulation. These studies suggest that CLN3 …
The Role Of Glutaminase 1 In Hiv-1 Associated Neurocognitive Disorders And In Brain Development, Yi Wang
The Role Of Glutaminase 1 In Hiv-1 Associated Neurocognitive Disorders And In Brain Development, Yi Wang
Theses & Dissertations
Glutaminase is the enzyme that converts glutamine into glutamate, which serves as a key excitatory neurotransmitter and one of the energy providers for cellular metabolism. Glutamate is essential for proper brain functioning but at excess levels, it is neurotoxic and has a key role in the pathogenesis of various neurodegenerative diseases, including HIV-1 associated neurocognitive disorders (HAND). However, the detailed mechanism of glutamate-mediated neurotoxicity remains unclear. In part I, we identified the regulation of glutaminase 1 (GLS1) in the central nervous system (CNS) of HAND animal models including HIV-Tat transgenic (Tg) mouse and HIVE-SCID mouse, since GLS1 is the dominant …