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The Journal of Cell Biology, Vol 46, 505-517, Copyright © 1970 by Rockefeller University Press

ARTICLE

RETARDATION OF PERIPHERAL NERVE MYELINATION IN MICE TREATED WITH INHIBITORS OF CHOLESTEROL BIOSYNTHESIS : A Quantitative Electron Microscopic Study



Frank A. Rawlins 1 and Betty G. Uzman 1

1 From the Children's Cancer Research Foundation and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115

The effect of two inhibitors of cholesterol biosynthesis, triparanol and AY 9944, on peripheral nerve myelination, was studied. Suckling mice were intraperitoneally injected with both drugs on 3 consecutive days and were sacrificed 6 hr after the last injection; others were suckled by an injected mother and sacrificed at 2frac12 days of age. A single mouse which had been injected with both drugs at 1, 2, and 3 days of age was sacrificed 2 wk after the last injection.

Membranous and crystalline intracytoplasmic inclusions were observed in the Schwann cells of the sciatic nerves of all the experimental animals. Both the number of unmyelinated single axons and the number of myelin lamellae around each myelinating axon in the sciatic nerves were recorded for treated mice and of mice suckled by treated mothers.

The sciatic nerve of the experimental mice contained a larger proportion of unmyelinated single axons and smaller numbers of myelin lamellae around the myelinating axons, when compared with age-matched controls. The results suggest that a decrease of endogenous cholesterol in suckling mice may affect peripheral nerve myelination in two ways: by retarding the "triggering" of myelination in unmyelinated axons and by decreasing the rate of myelination already in progress.

Submitted on December 12, 1969
Revised on March 26, 1970


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