title: Lipopolysaccharide-induced nigral inflammation leads to increased IL-1β tissue content and expression of astrocytic glial cell line-derived neurotrophic factor.
abstract: Reactive gliosis and inflammatory change is a key component of nigral dopaminergic cell death in Parkinson's disease (PD). Astrocyte derived glial cell line-derived neurotrophic factor (GDNF) promotes the survival and growth of dopaminergic neurones and it protects against or reverses nigral degeneration induced by 6-OHDA and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in rodents and primates. But the effect of increased levels of pro-inflammatory cytokines on the release of GDNF is unknown. This study examined the relationship between release of tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and the expression of GDNF in rats following nigral lipopolysaccharide (LPS) administration. Acute nigral administration of LPS led to marked elevation of IL-1β but insignificant TNF-α tissue content and to a prominent expression of GDNF immunoreactivity in astrocytes but not microglia. The results suggest that inflammation is not only involved in neuronal loss but could promote neuronal survival through increased release of GDNF following up-regulation of IL-1β.
authors.affiliation: Neurodegenerative Disease Research Centre, Institute of Pharmaceutical Sciences, School of Biomedical Sciences, King's College London, SE1 1UL London, UK. m.iravani@kcl.ac.uk
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: Iravani
authors.forename: Mona
authors.initials: M
authors.lastname: Sadeghian
authors.forename: Clement C M
authors.initials: CC
authors.lastname: Leung
authors.forename: Peter
authors.initials: P
authors.lastname: Jenner
authors.forename: Sarah
authors.initials: S
authors.lastname: Rose
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D005911:Gliosis / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D017628:Microglia / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha