Chapter 11 - The MPTP Mouse Model of Parkinson's Disease: the True, the False, and the Unknown

Abstract

This chapter provides a detailed discussion on the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson's disease (PD). MPTP is the only known dopaminergic neurotoxin capable of causing a clinical picture in both humans and monkeys that is indistinguishable from PD. While its handling requires a series of precautions, the use of MPTP is straightforward since it does not require any particular piece of equipment such as a stereotaxic frame. Moreover, it does not require surgery on live animals as needed for 6-hydroxydopamine or rotenone. MPTP produces a reliable and reproducible lesion of the nigrostriatal dopaminergic pathway after its systemic administration, which is often not the case for other publicized poisons. While MPTP monkeys remain the gold standard for the preclinical testing of new therapies for PD, most of the studies geared toward unraveling the mechanisms underlying the demise of dopaminergic neurons have been performed primarily in mice. This chapter focuses on several questions about MPTP mouse model and shows that many of the popular objections made about this model are false. This chapter also gives an opportunity to stress some of the important limitations of this model and to discuss how these may impact the interpretations of one's data.