Lack of nigrostriatal pathology in a rat model of proteasome inhibition.
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.
Manning-Boğ
Amy B
AB
Department of Basic Research, The Parkinson's Institute, Sunnyvale, CA, USA. amanning-bog@thepi.org
Reaney
Stephen H
SH
Chou
Vivian P
VP
Johnston
Louisa C
LC
McCormack
Alison L
AL
Johnston
Jennifer
J
Langston
J William
JW
Di Monte
Donato A
DA
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
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