Are the early stages of Parkinson’s disease accompanied by motor improvements?

Parkinson`s disease (PD) is the 2nd most common neurodegenerative disorder, characterized by a preferential loss of the dopaminergic (DA) neurons of the substantia nigra pars compacta (SNpc), projecting to the striatum. This loss results in a decrease in dopamine content in the striatum, and in motor and movement impairments.

1-Methyl­-4­-phenyl­-1,2,3,6­-tetrahydropyridine (MPTP) is one of the most commonly used reagents used to induce parkinsonism in animals. Though this model works very well in primates, in rodents the assessments of MPTP effects are con­troversial.

Mitochondrial carrier homolog 2 (MTCH2) is an important regulator of mitochondrial apoptosis and metabolism. Our lab has shown that loss of MTCH2 results in a compensatory increase in mitochondrial function. To assess a possible role for MTCH2 in the progression of PD, we created a SNpc-specific MTCH2 knockout in mice and assessed the effects of MPTP administration on these mice.

Our results suggest that MPTP-induced parkinsonism in mice is accompanied by motor improvements and might represent early stages of PD. In addition, loss of mitochondrial MTCH2 seems to mimic the MPTP effect, possibly by a compensatory increase in mitochondrial function, which may lead to motor improvements.