Inhibition of protein synthesis during CNS myelination produces focal accumulations of membrane vesicles in oligodendrocytes

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Abstract
Summary Optic nerves ofXenopus tadpoles were exposed to cycloheximide to identify changes that occur during CNS myelin membrane formation when protein synthesis is inhibited. Groups of stage 51–56 tadpoles were immersed in either 10 or 20 μg ml−1 cycloheximide, and at specified times between 12 and 18 h after initial immersion tadpoles were killed and their optic nerves prepared for ultrastructural analysis. As early as 12h there were alterations in oligodendrocytes from treated animals compared with control animals. The number of polyribosomes in the perikarya and cell processes was greatly reduced and the rough endoplasmic reticulum was disorganized. Mitochondria and microtubules were normal in appearance. Many oligodendroglial tongue processes at the inner margin of the myelin sheath were enlarged, occasionally indented the axon and were filled with vesicular profiles. Vesicles were noted in other cytoplasmic regions of oligodendrocytes and focal changes in the lamellar structure of myelin were found in paranodal regions. The internodal portions of the myelin sheath, axons and astrocytes appeared normal. Polyacrylamide gels of optic nerves showed that the incorporation of35S-methionine into polypeptides had been almost completely inhibited by treatment with cycloheximide. These observations suggest that cycloheximide, by inhibiting synthesis of myelin proteins, alters the ability of oligodendrocytes to incorporate membrane components into CNS myelin sheaths.