Pramipexole protects against MPTP toxicity in non-human primates.
The neurotoxin MPTP induces nigral dopaminergic cell death in primates and produces a partial model of Parkinson's disease (PD). Pramipexole is a D2/D3 dopamine receptor agonist used in the symptomatic treatment of PD, and which also protects neuronal cells against dopaminergic toxins in vitro. We now demonstrate that pramipexole partially prevents MPTP toxicity in vivo in a primate species. Common marmosets were repeatedly treated with pramipexole either before, coincidentally with, or after low-dose MPTP treatment designed to induce a partial lesion of the substantia nigra. Animals pretreated with pramipexole had a significantly greater number of surviving tyrosine hydroxylase (TH) positive neurones in the pars compacta of the substantia nigra. Pramipexole pretreatment also prevented degeneration of striatal dopamine terminals. Treatment with pramipexole concurrently with MPTP or following MPTP did not prevent TH-positive cell loss. Pramipexole pretreatment appears to induce adaptive changes that protect against dopaminergic cell loss in primates.
Iravani
Mahmoud M
MM
Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London, UK.
Haddon
Claire O
CO
Cooper
J Mark
JM
Jenner
Peter
P
Schapira
Anthony H
AH
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D052160:Benzothiazoles; D002144:Callithrix; D002452:Cell Count / Q000379:methods; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D020267:MPTP Poisoning / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D000077487:Pramipexole; D013844:Thiazoles / Q000008:administration & dosage*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000975:Antioxidants; D052160:Benzothiazoles; D013844:Thiazoles; D000077487:Pramipexole; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase