Monoamine oxidase (MAO), a major intracellular enzyme which degrades biogenic amines in mammalian brain, has been proposed to participate in a variety of psychiatric and neurological disorders involving catecholamine abnormalities, including schizophrenia, affective disorders, and Parkinson's disease. Past studies of MAO in schizophrenia have focused on platelet MAO (MAO B) because of its accessibility; of the few studies which have analyzed MAO activity in the human brain, only regional comparisons of homogenized tissue have been attempted. We propose to undertake with newly available reagents a comprehensive study of the regional and cellular localization of MAO A and B in monkey brain and human autopsy brain from normals and schizophrenics by immunoperoxidase staining with our MAO A- and B-specific monoclonal antibodies. Concurrently, we will identify MAO-rich cell types and brain regions of importance to schizophrenia by staining the same or alternate sections for serotonin, dopamine-beta-hydroxylase, phenylethanolamine-N-methyltransferase, tyrosine hydroxylase, and glial fibrillary acidic protein. MAO in localized regions will be subjected to computer-quantitated immunohistochemical analysis in stained, fixed tissue, and radioenzymatic activity assays and radioimmunoassays of enzyme concentration in extracts of tissue preserved by freezing. Electron microscopy will be used to determine the orientation of MAO in the inner and outer surfaces of the outer mitochondrial membrane. After studies in whole monkey and normal human brains are complete, we will compare autopsy material from age- and sex-matched normal controls and patients diagnosed as having Parkinson's disease and schizophrenia. The Parkinson's studies will help to validate our new methodologies in a disease with well documented anatomical and biochemical abnormalities in specific neural tracts, and may reveal important information about the role of MAO in this disorder. The studies of schizophrenia will provide detailed information about the cellular and regional distribution of MAO (which is thought to be deficient in those at risk for this disease) in the specific neural tracts proposed to be involved in the etiology of this disease. Studies in monkeys will help to evaluate the possible effects of neuroleptics on MAO distribution and cellular localization in brains of schizophrenics treated with these drugs.
| Bach, A W; Lan, N C; Johnson, D L et al. (1988) cDNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties. Proc Natl Acad Sci U S A 85:4934-8 |
