Expression of striatal preprotachykinin mRNA in symptomatic and asymptomatic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-exposed monkeys is related to parkinsonian motor signs

Striatal preprotachykinin (PPT) gene expression and [H-3] mazindol binding were examined in monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyr idine (MPTP). Some animals (n = 5) became moderately to severely parkinsoni an after receiving large doses of MPTP over 9-30 d and remained symptomatic for a relatively short time (3 weeks to 3 months; acutely symptomatic grou p). A second group of animals (n = 5) received low doses of MPTP (1.5-12 mo nths), developed cognitive impairments but displayed no gross motor deficit s (asymptomatic group), and were killed 3-12 months after their final dose of MPTP. Other animals became moderately to severely parkinsonian after rec eiving escalating doses of MPTP (>6 months; n = 4) or high doses of MPTP (< 1 month; n = 1) and remained symptomatic for 2.5-5.75 years (chronically sy mptomatic group). All MPTP-treated animals had extensive losses of [H-3] ma zindol binding in dorsal striatal sensorimotor regions with asymptomatic an imals generally having a lesser degree of damage. However, PPT mRNA levels differed sharply among treatment groups. Symptomatic animals (acutely and c hronically parkinsonian) had significantly decreased PPT mRNA levels in mos t striatal regions. In asymptomatic animals, PPT mRNA expression was not si gnificantly different from that measured in control animals, despite decrea ses in [H-3] mazindol binding in some striatal regions of similar magnitude to those observed in symptomatic animals. These observations suggest that PPT gene expression may be directly related to expression of parkinsonian m otor symptomatology regardless of duration of MPTP exposure, duration of th e parkinsonism, or extent of dopamine denervation. These results imply that the direct striatal output circuit may have a greater contribution to expr ession of parkinsonian symptomatology than proposed previously.