Abstract
We studied the control of sterol synthesis during myelination of central nervous system in culture. Explants of fetal mouse spinal cord were cultured for 3-30 days in vitro (DIV). Myelination was visible by electron micriscopy at 3 DIV, and by bright-field light microscopy beginning at 6 DIV. All explants were heavily myelinated by 15 DIV. Specific activity of 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNP) increased rapidly until 15 DIV. The rate of incorporation of [1-14C]acetate into sterol was greatest at 12 DIV, more than double that at 4 and 22 DIV. Specific activity of the mevalonate synthesizing enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase) was greatest at 11 DIV, threefold greater than at 6 and 30 DIV. Previous studies in fibroblasts and other non-neural tissues had shown that deprivation of exogenous lipid caused a rapid increase in HMG CoA reductase activity. In contrast, when the spinal cord explants were incubated for 24 h in a lipid-deficient medium, there was either a marked decrease in specific activity of HMG CoA reductase (at 6, 15 and 30 DIV), or no change in enzyme activity (at 11 DIV).
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