Nigrostriatal reduction of aromatic L-amino acid decarboxylase activity inMPTP-treated squirrel monkeys: In vivo and in vitro investigations

Aromatic L-amino acid decarboxylase (AAAD) activity was examined in vivo wi th positron emission tomography (PET) using 6-[F-18]fluoro-L-DOPA (FDOPA) i n squirrel monkeys lesioned with graded doses of the neurotoxin 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine (MPTP). In vitro biochemical determinatio ns of AAAD activity in caudate, putamen, substantia nigra, and nucleus accu mbens were performed in the same animals to establish a direct comparison o f in vivo and in vitro measurements. In vivo and in vitro AAAD activities i n caudate/putamen were substantially reduced in animals treated with the hi ghest dose of MPTP (2.0 mg/kg), The percent change in the striatal FDOPA up take (K-i) and decarboxylation rate constant (k(3)) values resulting from M PTP treatment showed highly significant correlations with in vitro-determin ed AAAD activities. However, decarboxylase rates within individual animals presented as similar to 10-fold difference between in vivo and in vitro val ues. Lower in vivo k(3) measurements may be attributed to several possibili ties, including transport restrictions limiting substrate availability to A AAD within the neuron. In addition, reductions in AAAD activity in the subs tantia nigra did not parallel reductions in AAAD activity within the striat um, supporting the notion of a nonlinear relationship between nigrostriatal cell degeneration and terminal losses. This work further explores the role of AAAD in Parkinson's disease, a more important factor than previously th ought.