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dc.contributor.advisorGiulio Taglilatela Ph.D.en_US
dc.creatorMichael Thomasen_US
dc.date.accessioned2011-12-20T16:05:06Z
dc.date.available2008-06-17en_US
dc.date.available2011-12-20T16:05:06Z
dc.date.created2005-07-28en_US
dc.date.issued2005-07-13en_US
dc.identifier.otheretd-07282005-112232en_US
dc.identifier.urihttp://hdl.handle.net/2152.3/195
dc.description.abstractIncreased 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.mediumelectronicen_US
dc.language.isoengen_US
dc.rightsCopyright © 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.subjectoxidative stressen_US
dc.subjectneurodegenerationen_US
dc.subjectAlzheimers Diseaseen_US
dc.titleEffects of tumor necrosis factor alpha on nitric oxide synthase in nerve growth factor-responding cellsen_US
dc.type.materialtexten_US
dc.type.genredissertationen_US
thesis.degree.namePhDen_US
thesis.degree.levelDoctoralen_US
thesis.degree.grantorThe University of Texas Medical Branchen_US
thesis.degree.departmentNeuroscience and Cell Biologyen_US
dc.contributor.committeeMemberTim Cowen Ph.D.en_US
dc.contributor.committeeMemberRegino Perez-Polo Ph.D.en_US
dc.contributor.committeeMemberRandall Urban M.D.en_US
dc.contributor.committeeMemberNorbert Herzog Ph.D.en_US
dc.contributor.committeeMemberAnne Andorn M.D.en_US


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