| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1987: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1986: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1985: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
To elucidate the physiological role of D-amino acid oxidase (DAO), a flavin-containing peroxisomal enzyme, in the mammalian central nervous system, it isimportant to explore the histological localization of DAO and its correlation to the oxidizing activity of thiazolidine-2-carboxylate (TC), which is an adduct of cysteamine and glyoxylate and is believed to be a physiological substrate for DAO.
Using serial fixed sections, we carried out a histochemical study on DAO in the whole brain of rat by a sensitive peroxidase-coupled procedure which we devised for histochemical detection of DAO activity. This method is based on the intensifying effect of nickel ions on diaminobenzidinebased product formation with peroxidase. DAO activity was found to be localized exclusively in the lower brain stem, cerebellum and spinal cord, and to be present only in astrocytes and Bergmann glial cells, but not in neuronal components, endothelial cells or ependymal cells. Form electron microscopic observations, the greater proportion of DAO activity was present in the glial spaces around various kinds of synapses. We also applied the above technique for the detection of TC oxidase activity. The localizations of this oxidase activity in the kidney, liver and brain of rat were in accord with those of DAO. On the other hand, the activity of D-aspartate oxidase, another peroxisomal flavoenzyme, was found in the endbrain in which DAO activity was not detectable.
The above results clearly demonstrate the regional differentiation of astrocytes and the uneven distribution of peroxisomal enzymes in the brain. It is also suggested the possibility that DAO is involved in the metabolic regulation by controlling the intracellular level of cysteamine and its metabolite, an oxalyl thiol ester, which are known to be metabolic effectors.
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