A quantitative electron microscopic analysis of myelination in the optic nerve of suckling rats treated with an inhibitor of cholesterol biosynthesis

Summary The effect of AY-9944, an inhibitory cholesterol biosynthesis, on the myelination of the optic nerve of rats was studied. Suckling rats were injected intraperitoneally with the drug every other day from birth, and were sacrificed at 10, 20 and 30 days of age together with littermate controls. The analysis is based on counting, at the electron-microscope level, the number of unmyelinated axons and the number of myelin lamellae surrounding each myelinating axon. The results indicate that a decrease in endogenous cholesterol by AY 9944, induced an overall retardation of the myelination process in the optic nerve: a larger proportion of myelinated axons and smaller number of myelin lamellae around the myelinating axons, when compared with the littermate controls, was observed. Exogenous cholesterol from the maternal milk did not compensate for a lack in endogenous cholesterol.Degenerating myelin sheaths were frequently seen in the experimental optic nerves at 20 and 30 days of age. Numerous membranous, intracytoplasmic drug-induced inclusions were found at all ages studied. Acknowledgements. The author is particularly indebted to Dr. B. G. Uzman and Dr. G. M. Villegas for their valuable discussion and suggestions. He wishes also to thank Mr. F. Paredes, Mr. J. Aristimuño and Miss Marcia Escala for their technical assistance; Mr. J. Bigorra for the photographic aid, and Miss Sonia Rodríguez for her secretarial help.