Basic neuroscienceA quantitative approach to developing Parkinsonian monkeys (Macaca fascicularis) with intracerebroventricular 1-methyl-4-phenylpyridinium injections

- Through this new method, the researcher can quantitatively develop PD monkey model of specific PD stage in a specified time period.
- The monkeys have stable PD symptoms, low individual variation and good general conditions.
- This new PD monkey model also has typical pathological changes of Parkinsonism.

BackgroundNon-human primate Parkinson's disease (PD) models are essential for PD research. The most extensively used PD monkey models are induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, the modeling processes of developing PD monkeys cannot be quantitatively controlled with MPTP. Therefore, a new approach to quantitatively develop chronic PD monkey models will help to advance the goals of “reduction, replacement and refinement” in animal experiments.New methodA novel chronic PD monkey models was reported using the intracerebroventricular administration of 1-methyl-4-phenylpyridinium (MPP+) in Cynomolgus monkeys (Macaca fascicularis).ResultsThis approach successfully produced stable and consistent PD monkeys with typical motor symptoms and pathological changes. More importantly, a sigmoidal relationship (Y = 8.15801e−0.245/x; R = 0.73) was discovered between PD score (Y) and cumulative dose of MPP+ (X). This relationship was then used to develop two additional PD monkeys under a specific time schedule (4 weeks), with planned PD scores (7) by controlling the dose and frequency of the MPP+ administration as an independent validation of the formula.Comparison with existing method(s)We developed Parkinsonian monkeys within controlled time frames by regulating the accumulated dose of MPP+ intracerebroventricular administered, while limiting side effects often witnessed in models developed with the peripheral administration of MPTP, makes this model highly suitable for treatment development.ConclusionsThis novel approach provides an edge in evaluating the mechanisms of PD pathology associated with environmental toxins and novel treatment approaches as the formula developed provides a “map” to control and predict the modeling processes.