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dc.contributor.authorIravani, Mahmoud M.
dc.contributor.authorLeung, Clement C. M.
dc.contributor.authorSadeghian, Mona
dc.contributor.authorHaddon, C. O.
dc.contributor.authorRose, Sarah
dc.contributor.authorJenner, P.
dc.date.accessioned2013-06-27T07:46:53Z
dc.date.available2013-06-27T07:46:53Z
dc.date.issued2005-07
dc.identifier.citationIravani , M M , Leung , C C M , Sadeghian , M , Haddon , C O , Rose , S & Jenner , P 2005 , ' The acute and the long-term effects of nigral lipopolysaccharide administration on dopaminergic dysfunction and glial cell activation ' , European Journal of Neuroscience , vol. 22 , no. 2 , pp. 317-330 . https://doi.org/10.1111/j.1460-9568.2005.04220.x
dc.identifier.issn0953-816X
dc.identifier.otherPURE: 735458
dc.identifier.otherPURE UUID: efc5c89d-a358-4b3f-86a9-f2f5aa8fa98d
dc.identifier.otherWOS: 000230601300004
dc.identifier.otherScopus: 23244449641
dc.identifier.otherORCID: /0000-0002-4905-9682/work/32997590
dc.identifier.urihttp://hdl.handle.net/2299/10970
dc.description.abstractSustained reactive microgliosis may contribute to the progressive degeneration of nigral dopaminergic neurons in Parkinson's disease (PD), in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposed human and in non-human primates. However, the temporal relationship between glial cell activation and nigral cell death is relatively unexplored. Consequently, the effects of acute (24 h) and chronic (30 days) glial cell activation induced by unilateral supranigral lipopolysaccharide (LPS) administration were studied in rats. At 24 h, LPS administration caused a marked reduction in the number of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra (SN) but striatal TH-ir was unaffected. By 30 days, the loss of TH-positive neurons in the LPS-treated nigra was no greater than at 24 h although a heterogeneous loss of striatal TH-ir was present. The loss of nigrostriatal neurons was of functional significance, as at 30 days, LPS-treated rats exhibited ipsiversive circling in response to (+)-amphetamine administration. At 24 h, there was a moderate increase in glial fibrillary acidic protein (GFAP)-ir astrocytes in the SN but a marked elevation of p47phox positive OX-42-ir microglia, and intense inducible nitric oxide synthase (iNOS)-ir and 3-nitrotyrosine (3-NT)-ir was present. However, by 30 days the morphology of OX-42-ir microglia returned to a resting state, the numbers were greatly reduced and no 3-NT-ir was present. At 30 days, GFAP-ir astrocytes were markedly increased in number and iNOS-ir was present in fibrillar astrocyte-like cells. This study shows that acute glial activation leading to dopaminergic neuron degeneration is an acute short-lasting response that does not itself perpetuate cell death or lead to prolonged microglial activation.en
dc.format.extent14
dc.language.isoeng
dc.relation.ispartofEuropean Journal of Neuroscience
dc.subjectinducible nitric oxide synthase (iNOS)
dc.subjectinflammation
dc.subjectParkinson's disease
dc.subjectreactive gliosis
dc.subjectstriatum
dc.subjectsubstantia nigra
dc.subjectNITRIC-OXIDE SYNTHASE
dc.subject1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MOUSE MODEL
dc.subjectSINGLE INTRANIGRAL INJECTION
dc.subjectNECROSIS-FACTOR-ALPHA
dc.subjectPARKINSONS-DISEASE
dc.subjectMICROGLIAL ACTIVATION
dc.subjectSUBSTANTIA-NIGRA
dc.subjectINDUCED NEUROTOXICITY
dc.subjectCEREBROSPINAL-FLUID
dc.subjectREACTIVE MICROGLIA
dc.titleThe acute and the long-term effects of nigral lipopolysaccharide administration on dopaminergic dysfunction and glial cell activationen
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, Veterinary and Food Sciences
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Life and Medical Sciences
dcterms.dateAccepted2005-07
rioxxterms.versionofrecordhttps://doi.org/10.1111/j.1460-9568.2005.04220.x
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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