CATECHOLAMINERGIC NEURONS IN MAN: AGING AND DISEASE

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Dysfunction of brain catecholamine (CA)-containing neurons has been linked to both neurologic and psychiatric disease (e.g. Parkinson's disease, Alzheimer's Senile Demewtia, and schizopnrenia). The CA neurons which have been related to such diseases are the midbrain dopamine (DA)-containing neurons of the substantia nigra and ventral tegmental area, and the norepinephrine (NE)-containing neurons of the locus coeruleus (LC). In the human brain, these CA-containing cells decrease in number with aging and especially so with Parkinson's disease. The long term goal of this project is to determine whether changes in CA cell number and/or receptor properties are involved in age- and disease-related changes in human behavior. As a preliminary to this goal, we will first gather normative data on (a) aging, (b) laterality, and (c) racial make-up of CA cell topographies and receptor properties. Second, we will examine parkinsonian brains to determine whether the particular disease symptoms (e.g. tremor, rigidity, akinesia, demential) are correlated with regional CA cell loss. A multidisciplinary approach, combining anatomy, biochemistry and neurology, will be used in this project. Anatomically, midbrain DA and LC-NE neurons will be identified in terms of their containing neuromelanin pigment and the CA synthesizing enzyme, tyrosine hydroxylase. These two CA nuclei will be reconstructed into a three-dimensional space with a state-of-the-art computer graphics system. Biochemically, 3H-spiperone binding in striatal and limbic/cortical DA regions will be used to assay postsynaptic DA receptor number and sensitivity. Neurologically, Parkinsonian patients will be clinically and quantitatively evaluated in terms of their specific disease symptomatology, and their brains subsequently examined anatomically and biochemically, as above. Such an analysis of these nuclei in the human brain will elucidate the basic anatomical features of these cell groups, document topographic changes which accompany aging, provide a possible neuronal basis for specific symptoms in Parkinson's disease, and provide a normative data-base for future research on catecholamine-implicated diseases.