title: Neuroprotective effects of riluzole in early phase Parkinson's disease on clinically relevant parameters in the marmoset MPTP model.
abstract: The present study evaluates neuroprotection in a marmoset MPTP (1-methyl-1,2,3,6-tetrahydropyridine) model representing early Parkinson's disease (PD). The anti-glutamatergic compound riluzole is used as a model compound for neuroprotection. The compound is one of the few protective compounds used in the clinic for a neurodegenerative disorder. Marmoset monkeys were randomized into three groups of six: 1) an MPTP group receiving a total MPTP dose of 7 mg/kg (4 injections over two weeks, s.c.) 2) a riluzole group receiving besides MPTP, a twice daily dose of riluzole (10 mg/kg, p.o.), starting one week before MPTP and continuing for one week after the final MPTP injection and 3) a control group receiving saline instead of MPTP and riluzole. The marmosets' Parkinsonian symptoms were scored daily and their activity level, hand-eye coordination, jumping behavior, axial turning and night sleep parameters were tested and recorded weekly. At three weeks following the last MPTP challenge, brains were dissected and dopamine levels in the striatum and the tyrosine hydroxylase (TH) expressing dopamine (DA) neurons in the substantia nigra (SN) were compared. MPTP affected all behavioral parameters and sleep architecture and induced a relatively mild (50%) decline of DA neurons in the substantia nigra (SN). Riluzole relieved the Parkinsonian signs, and improved the hand-eye coordination as well as turning ability. Moreover, riluzole prevented the impact of MPTP on sleep architecture and rapid eye movement behavioral disorder (RBD). Riluzole also increased the number of surviving DA neurons in MPTP-treated marmosets to 75%. However, riluzole did not prevent the MPTP-induced impairments on locomotor activity and jumping activity. In conclusion, reduction of excitotoxicity by riluzole appeared to be effective in reducing progressive neurodegeneration and relieved several clinically relevant PD symptoms in an animal model representing the early phase of PD.
authors.affiliation: BU CBRN Protection, TNO Defence, Security and Safety, Lange Kleiweg 137, PO Box 45, 2280 AA Rijswijk, The Netherlands. nellekeverhave@gmail.com
authors.forename: Peternella S
authors.initials: PS
authors.lastname: Verhave
authors.forename: Marjan J
authors.initials: MJ
authors.lastname: Jongsma
authors.forename: Roland M
authors.initials: RM
authors.lastname: Van Den Berg
authors.forename: Raymond A P
authors.initials: RA
authors.lastname: Vanwersch
authors.forename: August B
authors.initials: AB
authors.lastname: Smit
authors.forename: Ingrid H C H M
authors.initials: IH
authors.lastname: Philippens
mesh_terms: D000818:Animals; D002144:Callithrix; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D020267:MPTP Poisoning / Q000188:drug therapy*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019782:Riluzole / Q000494:pharmacology / Q000627:therapeutic use*; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D019782:Riluzole; D004298:Dopamine