Molecular and Cellular Neuroscience Commons^™

Understanding Exosomal Extracellular Vesicles And Morphine In The Neuropathology Of Human Immunodeficiency Virus And Differential Zika Virus Strain-Associated Pathology, Allen Caobi

FIU Electronic Theses and Dissertations

Exosomal Extracellular Vesicles (xEVs), integral to intercellular communication and regulation of immune responses, have functional effects based on their contents, which they transport to neighboring cells. However, in the context of infection, EV cargo can be modulated, by either infected or uninfected cells. We hypothesize that CNS-associated neuropathology, is partially, due to the cargo transported by the exosomes. We theorize that the cargo released from infected cell-derived xEVs may either facilitate or inhibit viral neuropathogenicity. Here we investigated xEVs in the case of two neurotropic viruses, Zika virus (ZIKV) and Human Immunodeficiency Virus (HIV). The hallmark characteristic of ZIKV-infection is …

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 …

Molecular Mechanism(S) Of Zika Virus Infection And Associated Neuropathogenesis, Chet Raj Ojha

FIU Electronic Theses and Dissertations

Zika virus (ZIKV), a mosquito-borne flavivirus, is known to induce various neurodevelopmental disorders including microcephaly and growth retardation in newborns from infected mothers. However, the exact mechanism of ZIKV-associated neurodevelopmental disorders is still unknown. The study was aimed at identifying the molecular mechanism(s) of ZIKV infection using in-vitro and in vivo methods. Using three isolated strains of ZIKV (MR766, R103451, and PRVABC59), we show that the Asian strains of ZIKV are more infective and toxic to glial cells and neurons compared to the African strain. Infection by PRVABC59 induces markedly higher release of inflammatory molecules; IP10, RANTES, IL-6, and IFN-β. …

Role Of Withaferin A As A Neuroprotectant Against Beta Amyloid Induced Toxicity And Associated Mechanism, Sneham Tiwari

FIU Electronic Theses and Dissertations

Neurological disorders are the biggest concern globally and ageing contributes in worsening the disease scenarios. In AD or AD like diseases, there is abnormal accumulation of extracellular amyloid beta produced due to abnormal processing of the transmembrane amyloid precursor protein, by β and γ-secretases. It spreads in the cortical and limbic regions of the brain leading to neuronal toxicity, impairment in memory and neurological functions. Aβ deposition in the CNS is common in aging HIV patients. Neurotoxic protein Tat, results in increased Aβ in combination with drugs of abuse cocaine. We examined the role of Withaferin A, against Aβ induced …

Hiv Tat And Morphine-Induced Neurodegeneration In A Beclin 1 Hemizygous Mouse Model, Jessica A. Lapierre

FIU Electronic Theses and Dissertations

Early in infection, HIV crosses the blood-brain barrier and induces neuropathology. Viral presence in the CNS coupled with secretion of neurotoxic proteins causes neuroinflammation, glial dysfunction, excitotoxicity, and neuronal death. Despite advances in combined antiretroviral therapy, HIV-infected patients present with a spectrum of cognitive and psychomotor deficits collectively referred to as HIV-associated neurological disorders (HAND). A subset of HAND patients abuses drugs such as opiates like heroin and morphine show an exacerbation and rapid progression of HIV neuropathology; however, the mechanisms of this synergy are not well understood. Autophagy is a lysosomal degradative process which eliminates and recycles cytosolic components …

Understanding Ten-Eleven Translocation-2 In Hematological And Nervous Systems, Feng Pan

FIU Electronic Theses and Dissertations

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems.

In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA …