Introduction to: Neurotoxin-based Nonhuman Primate Models of Parkinson's Disease

This chapter provides an overview of the neurotoxin-based nonhuman primate models of Parkinson's disease (PD). Recent studies on PD models have focused on the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The specific neurotoxic actions of MPTP are produced when it is metabolized by monoamine oxidase B into 1-methyl-4-phenylpyridinium (MPP+), a complex I mitochondrial neurotoxin with relative specificity for dopamine neurons in the substantia nigra. In species including mice and nonhuman primates where monoamine oxidase B is found in the brain, systemically administered MPTP crosses the blood brain barrier and is converted into MPP+. MPP+ toxicity selectively and robustly lesions the nigrostriatal dopamine system, replicating many features of PD. Administration of MPTP to nonhuman primates invariably targets the nigrostriatal dopamine pathway, primary neural system that degenerates in PD. Some models using MPTP however fail to replicate other key features of PD. The chapter discusses how the neural circuitry affected by MPTP-induced degeneration of the nigrostriatal dopamine system can be mapped and analyzed. The chapter also emphasizes that MPTP models do not replicate the long prodromal period preceding the expression of parkinsonian signs in many patients.