Neuroprotective effect of riluzole in a primate model of Parkinson's disease: behavioral and histological evidence.
Our study aimed to determine whether riluzole, which has shown efficacy as a disease-modifying agent in amyotrophic lateral sclerosis (ALS), is neuroprotective in a marmoset model of Parkinson's disease (PD). Reduction of energy demand by riluzole could be a rational neuroprotective strategy with good tolerability. The efficacy of riluzole was evaluated in marmosets by testing its ability to reduce MPTP-induced behavioral deficits and loss of dopaminergic nigral neurons. Marmosets were divided into two groups of four animals each: animals in Group 1 were injected twice with MPTP (2 mg/kg subcutaneous) and treated with riluzole (10 mg/kg per os b.i.d.), animals in Group 2 (controls) were injected with MPTP and with the vehicle of riluzole. A third group of marmosets which did not receive MPTP or riluzole drug was introduced for neurohistopathological studies (normal animals). Marmosets treated with riluzole preserved a better motor function and neurological performance through the 26 days of assessment when compared with the controls. Histologically, there was sparing of TH- and Nissl-stained nigral neurons and of TH-stained terminals in the striatum and the putamen in the group treated with riluzole compared to the controls. We conclude that riluzole protects dopaminergic neurons and reduces behavioral deficits in a marmoset model of PD.
Obinu
Maria C
MC
Neurodegenerative Disease Program, Research Center of Paris, Aventis Pharma, S.A. Vitry sur Seine, France. Marie-Carmen.Obinu@aventis.com
Reibaud
Michel
M
Blanchard
Véronique
V
Moussaoui
Saliha
S
Imperato
Assunta
A
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002144:Callithrix; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000009:adverse effects; D005260:Female; D007150:Immunohistochemistry; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009562:Nissl Bodies / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000188:drug therapy*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D011897:Random Allocation; D019782:Riluzole / Q000494:pharmacology / Q000627:therapeutic use*; D013378:Substantia Nigra / Q000187:drug effects
D015259:Dopamine Agents; D018696:Neuroprotective Agents; D019782:Riluzole; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine