Effects of Brain-derived Neurotrophic Factor on 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in Monkeys

Abstract

THE EFFECTS OF intrathecal infusion of brain-derived neurotrophic factor (BDNF) were examined in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian model in monkeys. Nine Japanese monkeys were divided randomly into three groups, an untreated control (n = 3), a BDNF group (n = 3), and a non-BDNF group (n = 3). Animals in the BDNF group received continuous intrathecal infusion of 10 ml of cell culture medium containing 10 μg of BDNF protein; the non-BDNF group received intrathecal infusion of the same culture medium without BDNF. To induce parkinsonian syndromes, a total of 1 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine was administered intravenously to each monkey in both the BDNF and non-BDNF groups. The neurological signs in the monkeys were monitored for 2 weeks and were scored according to the monkey parkinsonism rating scale; histological changes in the substantia nigra were evaluated after the 2-week observation period. The BDNF-treated animals remained asymptomatic during the 1st week and showed mild parkinsonism during the 2nd week, whereas the non-BDNF group showed typical parkinsonian syndrome during the 1st week, with deterioration in the 2nd week. Histological damage in the substantia nigra correlated well with the clinical features. Severe neuronal cell loss in the substantia nigra was observed in animals with severe parkinsonism (those in the non-BDNF group), whereas significantly less damage was observed in this region in the BDNF group. These findings suggest that BDNF may have a preventive effect on the neurological syndrome and the histological damage of the substantia nigra in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in monkeys.