Alterations in multiple tyrosine hydroxylase mRNAs 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 humans. We have previously reported that only monkeys and humans have multiple isoforms of tyrosine hydroxylase (TH), the first enzyme for dopamine biosynthesis, with only two TH mRNA isoforms, type 1 and type 2, being present in Macaca fascicularis. In the present study we have measured TH mRNA type 1 and 2 content in the substantia nigra, locus coeruleus, and adrenal gland of normal control monkeys and in MPTP-produced parkinsonian monkeys (Macaca fascicularis) using a newly developed, sensitive and quantitative assay based on the reverse transcription-polymerase chain reaction. Marked decreases in TH mRNA type 1 and 2 content 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 changes in TH isoforms in human Parkinson's disease.