MPTP induces dystonia and parkinsonism

TLDR

Striatal dopamine dysfunction is implicated in dystonia, is well established in parkinsonism, and dystonia often precedes parkinsonism in humans. The study proposes that striatal dopamine deficiency can lead to parkinsonism or dystonia. Baboons received intracarotid MPTP, which induced transient hemidystonia before hemiparkinsonism. After MPTP, baboons exhibited ipsilateral turning, then contralateral hemidystonia with extended limbs, which preceded hemiparkinsonism lasting up to 1.5 years, and these motor changes temporally matched reduced striatal dopamine and transient D2‑like receptor loss, suggesting additional factors modulate clinical expression.

Abstract

The pathophysiology of dystonia is unclear, but several clues implicate striatal dopamine dysfunction. In contrast, the causal relationship between striatal dopamine deficiency and parkinsonism is well defined. We now suggest that parkinsonism or dystonia may occur following striatal dopamine deficiency. Baboons treated with intracarotid 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) developed transient hemidystonia prior to hemiparkinsonism. The day after MPTP treatment, most animals had spontaneous ipsilateral turning. Within a few days, all developed contralateral hemidystonia, with the arm and leg extended and externally rotated. This transient dystonia preceded hemiparkinsonism with flexed posture, bradykinesia, and postural tremor that persisted for up to 1.5 years. Dystonia corresponded temporally with a decreased striatal dopamine content and a transient decrease in D₂-like receptor number. The time course of dystonia and parkinsonism is analogous to lower limb dystonia as the first, frequently transient, symptom of Parkinson9s disease in humans. The association of striatal dopamine deficiency with dystonia and parkinsonism implies that other factors influence clinical manifestations.