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dc.contributor.authorIravani, Mahmoud M.
dc.contributor.authorKashefi, K.
dc.contributor.authorMander, P.
dc.contributor.authorRose, S.
dc.contributor.authorJenner, P.
dc.date.accessioned2014-01-16T10:30:40Z
dc.date.available2014-01-16T10:30:40Z
dc.date.issued2002-03
dc.identifier.citationIravani , M M , Kashefi , K , Mander , P , Rose , S & Jenner , P 2002 , ' Involvement of inducible nitric oxide synthase in inflammation-induced dopaminergic neurodegeneration ' , Neuroscience , vol. 110 , no. 1 , pp. 49-58 . https://doi.org/10.1016/S0306-4522(01)00562-0
dc.identifier.issn0306-4522
dc.identifier.otherPURE: 735822
dc.identifier.otherPURE UUID: 23848ca0-bbd9-4823-8045-4cb623430df2
dc.identifier.otherWOS: 000174680200006
dc.identifier.otherScopus: 0036499736
dc.identifier.otherORCID: /0000-0002-4905-9682/work/32997597
dc.identifier.urihttp://hdl.handle.net/2299/12558
dc.description.abstractThe loss of dopaminergic neurotics in the substantia nigra with Parkinson's disease may result from inflammation-induced proliferation of microglia and reactive macrophages expressing inducible nitric oxide synthase (iNOS). We have investigated the effects of the supranigral administration of lipopolysaccharide on iNOS-immunoreactivity, 3-nitrotyrosine formation and tyrosine hydroxylase-immunoreactive neuronal number, and retrogradely labelled fluorogold-positive neurones in the ventral mesencephalon in male Wistar rats. Following supranigral lipopolysaccharide injection, 16-18 h previously, there was intense expression of NADPH-diaphorase and iNOS-immuno reactivity in non-neuronal, macrophage-like cells. This was accompanied by intense expression of glial fibrillary acidic protein-immuno reactive astrocytosis in the substantia nigra. There were also significant reductions in the number of tyrosine hydroxylase(50-60%)- and fluorogold (65-75%)-positive neurones in the substantia nigra. In contrast, tyrosine hydroxylase-immunoreactivity in the ventral tegmental area was not altered. Pre-treatment of animals with the iNOS inhibitor, S-methylisothiourea (10 mg kg(-1), i.p.), led to a significant reduction of lipopolysaccharide-induced cell death. Similar reduction of tyrosine hydroxylase-immunoreactivity and fluorogold-labelled neurotics in the substantia nigra following lipopolysaccharide administration suggests dopaminergic cell death rather than down-regulation of tyrosine hydroxylase. We conclude that the expression of iNOS- and 3-nitrotyrosine-immunoreactivity and reduction of cell death by S-methylisothiourea suggest the effects of lipopolysaccharide may be nitric oxide-mediated, although other actions of lipopolysaccharide (independent of iNOS induction) cannot be ruled out. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.en
dc.format.extent10
dc.language.isoeng
dc.relation.ispartofNeuroscience
dc.subjectdopaminergic neurones
dc.subjectinflammation
dc.subjectinducible nitric oxide synthase
dc.subjectlipopolysaccharide
dc.subjectParkinson's disease
dc.subjectPARKINSONS-DISEASE
dc.subjectSUBSTANTIA-NIGRA
dc.subjectGLIAL-CELLS
dc.subject1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP
dc.subjectINTRANIGRAL INJECTION
dc.subjectINDUCED NEUROTOXICITY
dc.subjectTYROSINE-HYDROXYLASE
dc.subjectNEUROLOGICAL DISEASE
dc.subjectOXIDATIVE DAMAGE
dc.subjectHUMAN BRAIN
dc.titleInvolvement of inducible nitric oxide synthase in inflammation-induced dopaminergic neurodegenerationen
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionPharmacology and Clinical Science Research
dc.contributor.institutionNeurodegenerative Diseases
dc.contributor.institutionAgriculture, Food and Veterinary Sciences
dc.description.statusPeer reviewed
dc.relation.school
dcterms.dateAccepted2002-03
rioxxterms.versionofrecordhttps://doi.org/10.1016/S0306-4522(01)00562-0
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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