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The Role Of Irf1 In The Brain And In Adaptive Responses Of Astrocytes, Andrew Hoskins
The Role Of Irf1 In The Brain And In Adaptive Responses Of Astrocytes, Andrew Hoskins
Theses and Dissertations
In neurodegenerative diseases, the CNS becomes inflamed through activation of pathways, including the NF-B pathway. Some of the therapies for those diseases target neuroinflammatory pathways. Here, we explore the mechanisms for the upregulation of a subset of genes following a restimulation of the NF-B pathway. We discover that this upregulation occurs independent of IRF1 expression and type 1 interferon signaling. A knockdown of IRF1 using siRNA and an inhibition of JAK proteins using inhibitor AG490 both had no effect on priming. A secreted factor was found to upregulate the expression of both this subset of genes and genes encoding pro-inflammatory …
Novel Role Of The Nociceptin System As A Regulator Of Glutamate Transporter Expression In Developing Astrocytes, Logan Meyer
Novel Role Of The Nociceptin System As A Regulator Of Glutamate Transporter Expression In Developing Astrocytes, Logan Meyer
Theses and Dissertations
Our previous results showed that oligodendrocyte development is regulated by both nociceptin and its G-protein coupled receptor, the nociceptin/orphanin FQ receptor (NOPR). The present in vitro and in vivo findings show that nociceptin plays a crucial conserved role in both human and rodent brain astrocytes, regulating the levels of the glutamate/aspartate transporter GLAST/EAAT1. This nociceptin-mediated response takes place during a critical developmental window that coincides with astrocyte maturation and synapse formation. GLAST/EAAT1 upregulation by nociceptin is mediated by NOPR and the downstream participation of a complex signaling cascade that involves the interaction of several kinase systems, including PI-3K/AKT, mTOR and …
Novel Mechanisms Regulating Cytokine-Induced Gene Expression In Astrocytes And Glioblastoma Cells, Lauren Bryan
Novel Mechanisms Regulating Cytokine-Induced Gene Expression In Astrocytes And Glioblastoma Cells, Lauren Bryan
Theses and Dissertations
Chronic inflammation in the brain results in the development of several CNS diseases, including Alzheimer’s and Parkinson’s diseases, multiple sclerosis, and tumors. IL-1, a pro-inflammatory cytokine released by activated microglia and astrocytes, instigates the expression of factors promoting the progression of these CNS disorders, including cytokines, chemokines, and components of matrix remodeling systems, such as the plasminogen activator system. IL-1 also increases the mRNA expression and activity of SphK, the enzyme that phosphorylates Sph to form S1P, a bio-active sphingolipid. This thesis demonstrates that IL-1 and S1P enhance the mRNA and protein expression of PAI-1 and uPAR, two key components …
Inflammation-Associated Gene Regulation In Primary Astrocytes, Glial Tumors And Cellular Differentiation, Katarzyna Marta Wilczynska
Inflammation-Associated Gene Regulation In Primary Astrocytes, Glial Tumors And Cellular Differentiation, Katarzyna Marta Wilczynska
Theses and Dissertations
This dissertation elucidates several independent molecular mechanisms that function in astrocytes and glial tumor cells, and suggest that developmental and inflammatory signals may contribute to the development of brain tumors. First, we analyzed the mechanism of TIMP-1 activation in astrocytes and glioblastoma cells. TIMP-1 expression is activated by IL-1, which is the major neuroinflammatory cytokine, via simultaneous activation of IKK/NF-kB and MEK3/6/p38/ATF-2 pathways in primary human astrocytes. In contrast to astrocytes, TIMP-1 is expressed at lower levels in glioblastomas, and is not regulated by IL-1 due to either dysfunctional IKK/NF-kB or MEK3/6/p38/ATF-2 activation. Thus, we propose a novel mechanism of …