Effects of dopamine denervation on striatal peptide expression in parkinsonian monkeys

In cynomolgus monkeys rendered parkinsonian by systemic injection of MPTP, severe cell losses were noted in the ventrolateral portion of the substantia nigra pars compacta (SNc), compared to a relative sparing of neurons in the ventral tegmental area (VTA) and dorsomedial portion of SNc. Most spared neurons in the SNc-VTA complex were found to contain the calcium binding protein calbindin (CaBP). At striatal levels the dopaminergic (DA) innervation, as visualized by tyrosine hydroxylase immunoreactivity, was markedly reduced in the 'sensorimotor' territory, variably affected in the 'associative' territory, and relatively well preserved in the 'limbic' territory. The immunoreactivity for enkephalin was enhanced and that for substance P was decreased in the sensorimotor territory, whereas the inverse was observed in the limbic territory. The distribution of the two peptides was highly heterogeneous in the associative territory. These findings suggest that the influence of the DA input on peptide expression varies from one striatal territory to the other, and that CaBP may protect midbrain DA neurons from MPTP toxicity.