Parkinson's Disease (PD) and the natural aging process share a number of biochemical mechanisms, including reduced function of dopaminergic systems. The present study aims to determine the extent that motor and behavioral changes in aged monkeys resemble
parkinsonism induced by the
neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The behavioral and physiological changes in PD are believed to result largely from selective depletion of
dopamine in the nigrostriatal system. In the present study, ten aged female monkeys were compared with three groups: 9 untreated young adult female monkeys, 10 young adult male monkeys and 13 older male monkeys that had been exposed to
MPTP. Trained observers, blind as to age and
drug condition and without knowledge of the hypotheses, scored the monkeys using the Parkinson's factor score (Parkscore), which has been validated by a high correlation with post mortem striatal
dopamine (DA) concentrations. The aged animals had higher scores on the Parkscore compared with the young adults, with most of its component behavioral items showing significance (
tremor, Eating Problems, Delayed initiation of movement, and Poverty of Movement).
L-Dopa and DA-agonists did not clearly reverse the principal measure of
parkinsonism. DA concentrations post mortem were 63% lower in 3 aged monkeys in the ventral putamen compared with 4 young adults, with greater reductions in putamen than in caudate (45%). We conclude that aged monkeys, unexposed to
MPTP, show a similar profile of
parkinsonism to that seen after the
neurotoxin exposure to
MPTP in young adult monkeys. The pattern of greater DA depletion in putamen than in caudate in aged monkeys is the same as in human
Parkinson's disease and contrasts with the greater depletion in caudate seen after
MPTP. Aged monkeys of this species reflect many facets of
Parkinson's disease, but like older humans do not improve with standard
dopamine replacement
pharmacotherapies.