PET studies of functional compensation in a primate model of Parkinsonʼs disease

Abstract

MPTP 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine is a neurotoxin that produces degeneration of nigrostriatal dopaminergic neurons and a chronic parkinsonian condition in primates. Positron emission tomography (PET) studies of rhesus macaques at various time points following unilateral MPTP administration demonstrated a different time course of degeneration in the dopaminergic terminals in the putamen and in the cell bodies in the substantia nigra, consistent with other evidence of retrograde degeneration. In addition, the substantia nigra showed a transient upregulation in dopaminergic function in the lesioned hemisphere indicating functional compensation. This plasticity has important implications for the therapeutic effects of growth factors and other potential treatments for neurodegenerative diseases.