ALTERATIONS IN MULTIPLE TYROSINE-HYDROXYLASE MESSENGER-RNAS IN THE SUBSTANTIA-NIGRA, LOCUS-COERULEUS AND ADRENAL-GLAND OF MPTP-TREATED PARKINSONIAN MONKEYS

Monkeys are known to be highly susceptible to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) which produces parkinsonism, as in huma ns. We have previously reported that only monkeys and humans have mult iple isoforms of tyrosine hydroxylase (TH), the first enzyme for dopam ine biosynthesis, with only two TH mRNA isoforms, type 1 and type 2, b eing present in Macaca fascicularis. In the present study we have meas ured TH mRNA type 2 and 2 content in the substantia nigra, locus coeru leus, and adrenal gland of normal control monkeys and in MPTP-produced parkinsonian monkeys (Macaca fascicularis) using a newly developed, s ensitive and quantitative assay based on the reverse transcription-pol ymerase chain reaction. Marked decreases in TH mRNA type 1 and 2 conte nt were observed, specifically in the substantia nigra of the monkeys with MPTP-parkinsonism compared to control monkeys. These results are similar to our recent data showing marked decreases in TH mRNA type 1, 2, 3 and 4 content in the substantia nigra of patients with Parkinson 's disease, and suggest that MPTP-treated monkeys closely replicate ch anges in TH isoforms in human Parkinson's disease.