Effects of tumor necrosis factor alpha on nitric oxide synthase in nerve growth factor-responding cells

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Effects of tumor necrosis factor alpha on nitric oxide synthase in nerve growth factor-responding cells

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dc.contributor.advisor Giulio Taglilatela Ph.D. en_US
dc.creator Michael Thomas en_US
dc.date.accessioned 2011-12-20T16:05:06Z
dc.date.available 2008-06-17 en_US
dc.date.available 2011-12-20T16:05:06Z
dc.date.created 2005-07-28 en_US
dc.date.issued 2005-07-13 en_US
dc.identifier.other etd-07282005-112232 en_US
dc.identifier.uri http://hdl.handle.net/2152.3/195
dc.description.abstract Increased cytokine levels have been observed in post mortem brains of Alzheimer Disease (AD) patients accompanied by a decrease in nerve growth factor (NGF)-responsive cholinergic neurons. I report a synergistic effect of the cytokine tumor necrosis factor alpha (TNFa) and NGF on expression of nitric oxide synthase (NOS), in rat pheochromocytoma PC12 cells. NGF/TNFa-promoted iNOS can be toxic in PC12 cells. Using PC12 cell mutants lacking the low affinity p75NTR receptor, we also demonstrate that this receptor is required to mediate iNOS expression, likely acting through the transcription factor nuclear factor kappa B (NF-kB). To determine if specific regions of the brain display a selective susceptibility to TNFa enhanced iNOS expression, I investigated the effects of in vivo stereotaxic injections of recombinant rat TNFa into the fourth ventricle of adult male C57BL/6 mice. There was a robust induction of iNOS expression following the injection of TNFa, which was restricted to the basal forebrain and hippocampus. No iNOS expression was detected in the striatum, or cerebellum. Determining whether the role of TNFa is one key to the selective neurodegeneration of NGF-responsive neurons in may allow for novel therapeutic strategies. en_US
dc.format.medium electronic en_US
dc.language.iso eng en_US
dc.rights Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works. en_US
dc.subject oxidative stress en_US
dc.subject neurodegeneration en_US
dc.subject Alzheimers Disease en_US
dc.title Effects of tumor necrosis factor alpha on nitric oxide synthase in nerve growth factor-responding cells en_US
dc.type.material text en_US
dc.type.genre dissertation en_US
thesis.degree.name PhD en_US
thesis.degree.level Doctoral en_US
thesis.degree.grantor The University of Texas Medical Branch en_US
thesis.degree.department Neuroscience and Cell Biology en_US
dc.contributor.committeeMember Tim Cowen Ph.D. en_US
dc.contributor.committeeMember Regino Perez-Polo Ph.D. en_US
dc.contributor.committeeMember Randall Urban M.D. en_US
dc.contributor.committeeMember Norbert Herzog Ph.D. en_US
dc.contributor.committeeMember Anne Andorn M.D. en_US

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