Inhibitors of cholesterol synthesis and myelin formation

Inhibitors of cholesterol biosynthesis AY 9944 and 20,25 diazacholesterol were administered by stomach tube to suckling rats in varying doses during the time of rapid myelination (15–22 days of age). Purified myelin was prepared from the brains and spinal cords, and the sterol content analyzed. Up to 50% of the myelin sterol consisted of desmosterol in rats treated with 20,25 diazacholesterol, while 7-dehydrocholesterol comprised at least one third of the myelin sterol in rats administered AY 9944. Myelin from rats treated with both compounds contained desmosterol, 7-dehydrocholesterol, Δ^5,7,24 cholestatriene-3-β-ol and an unknown sterol, the four comprising about 45% of the total sterol. The proportion of phospholipid: galactolipid-total sterol in myelin from the drug-treated rats was not significantly different from the normal, although much less myelin was recovered. Brain and spinal cord slices from 22 to 25-day rats pretreated with inhibitors showed decreased uptake of U-¹⁴C-glucose into all myelin components. The decreased uptake was approximately proportional in all lipids and the protein was also affected. It is proposed that myelin composition is fixed, and that a deficiency of one of the lipid components will limit the assembly of the whole lipid portion of the membrane. Presented at the AOCS Meeting, San Francisco, April 1969.