title: Lack of nigrostriatal pathology in a rat model of proteasome inhibition.
abstract: Systemic administration of ubiquitin-proteasome system inhibitors to rodents has been reported to induce certain behavioral and neuropathological features of Parkinson's disease. The goal of this study was to replicate these observations by administering a proteasome inhibitor (PSI) to rats using McNaught and colleagues' protocol. No alterations in locomotor activity or striatal dopamine and its metabolites were observed. Differences in nigral dopaminergic cell number between proteasome inhibitor- and vehicle-treated rats and inclusion bodies were not found. Extending the time of survival after administration and using different solvents failed to alter results, indicating this proteasome inhibitor does not consistently produce the selective toxicity and pathological hallmarks characterizing Parkinson's disease.
authors.affiliation: Department of Basic Research, The Parkinson's Institute, Sunnyvale, CA, USA. amanning-bog@thepi.org
authors.forename: Amy B
authors.initials: AB
authors.lastname: Manning-Boğ
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Reaney
authors.forename: Vivian P
authors.initials: VP
authors.lastname: Chou
authors.forename: Louisa C
authors.initials: LC
authors.lastname: Johnston
authors.forename: Alison L
authors.initials: AL
authors.lastname: McCormack
authors.forename: Jennifer
authors.initials: J
authors.lastname: Johnston
authors.forename: J William
authors.initials: JW
authors.lastname: Langston
authors.forename: Donato A
authors.initials: DA
authors.lastname: Di Monte
mesh_terms: D000818:Animals; D015415:Biomarkers; D002452:Cell Count; D015853:Cysteine Proteinase Inhibitors / Q000633:toxicity*; D004121:Dimethyl Sulfoxide; D000431:Ethanol; D008297:Male; D017072:Neostriatum / Q000378:metabolism / Q000473:pathology*; D009842:Oligopeptides / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; D012997:Solvents; C090535:benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal; D000431:Ethanol; D014446:Tyrosine 3-Monooxygenase; D004121:Dimethyl Sulfoxide