Studies on the pathogenesis of multiple sclerosis: 2′,3′-cyclic nucleotide 3-phosphohydrolase as marker of demyelination and correlation of findings with lysosomal changes

Abstract

2′,3′-Cyclic nucleotide 3-phosphohydrolase, an enzyme proven in earlier studies to be associated with myelin, was used as indicator of demyelination in autopsy specimens of brain in 8 cases of multiple sclerosis and 2 of subacute sclerosing panencephalitis. Our results revealed that areas which showed demyelination on light microscopy showed also decreased phosphohydrolase values. The activity of phosphohydrolase increased in areas immediately outside plaques. These results compared well with cerebroside and other lipid data. However it was found that there was some discrepancy between lipid amounts and phosphohydrolase activity. Some areas where phosphohydrolase values were 3–4 times lower than in corresponding control specimens showed only half of the normal cerebroside content. The so-called normal white matter outside plaques did not show any constant decrease of phosphohydrolase activity but our material is too limited for any conclusion to be drawn. Our second major finding in this study was an increased response of lysosomes in areas where phosphohydrolase or lipid data did not reveal significant pathological changes. These results suggest that before demyelination begins there is a cellular response, possibly in glial cells, and demyelination seems to be only one of the consequences of this response.