Absence of inclusion body formation in the MPTP mouse model of Parkinson's disease.
Formation of alpha-synuclein aggregation and Lewy bodies (LBs) are hallmarks of Parkinson's disease (PD) and other related diseases. The dopaminergic neurotoxin, MPTP, replicates many of the pathological signs and motoric features of PD in primates and rodents by selective destruction of dopamine (DA) neurons of the substantia nigra. In this study, groups of adult wild-type C57BL6 mice were treated with MPTP either acutely (20 mg/kg, every 2 h x 4 for 1 day), semi-chronically (30 mg/kg/day for 5 days), or chronically (25 mg/kg MPTP with 250 mg/kg probenecid 2 times/week for 5 weeks). Mice brains were collected and processed at various time points for immunohistochemistry and HPLC assays. Our data showed that although there is a significant decrease in DA content and its metabolites and tyrosine hydroxylase immunoreactivity, there is no inclusion body formation following the various MPTP treatment regimens.
Shimoji
Mika
M
Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Suite 731, Baltimore, MD 21205, USA.
Zhang
Li
L
Mandir
Allen S
AS
Dawson
Valina L
VL
Dawson
Ted M
TM
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D002479:Inclusion Bodies / Q000378:metabolism*; D020267:MPTP Poisoning / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051843:Synucleins; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; C497605:Snca protein, mouse; D051843:Synucleins; D025801:Ubiquitin; D051844:alpha-Synuclein; D015102:3,4-Dihydroxyphenylacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid