Sterol synthesis by myelinating cultures of mouse spinal cord

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 microscopy 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, then more slowly. Explant sterol content rose more than threefold between 5 and 30 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).