QUANTIFICATION OF MESSENGER-RNA OF TYROSINE-HYDROXYLASE AND AROMATIC L-AMINO-ACID DECARBOXYLASE IN THE SUBSTANTIA-NIGRA IN PARKINSONS-DISEASE AND SCHIZOPHRENIA

Using the reverse transcription-polymerase chain reaction (RTPCR), we developed a sensitive and quantitative method to detect all four types of human tyrosine hydroxylase (TH) mRNAs in the human brain (substantia nigra). All four types of TH mRNAs were found in the substantia nigra in the control brains examined, and the ratio of type-1, type-2, type-3, and type-4 mRNAs to the total amount of TH was 45, 52, 1.4, and 2.1%, respectively. The average amount of total TH mRNA in the normal brain (substantia nigra) was 5.5 amol of TH mRNA per mu g of total RNA. The ratios of four TH isoforms were not altered significantly in Parkinson's disease or schizophrenia. Further we measured the relative amount of aromatic L-amino acid decarboxylase (AADC) and beta-actin mRNAs in the brain samples. TH and AADC mRNAs were highly correlated in the control cases. We found that parkinsonian brains had very low levels of all four TH isoforms and AADC mRNAs in the substantia nigra compared with control brains, while no significant differences were found between schizophrenic brains and normal ones. Since the decrease in AADC mRNA was comparable to that in TH mRNA, the alteration of TH in Parkinson's disease would not be a primary event, but it would reflect the degeneration of dopaminergic neurons in the substantia nigra. This is the first reported measurement of mRNA contents of TH isoforms and AADC in Parkinson's disease and schizophrenia.