Summary
Intraperitoneal injections of a hypocholesterolemic drug, AY9944 produced neuronal cytoplasmic inclusions in the brain of Wistar strain of rats.
The inclusions were numerous and larger in size in the younger age groups but gradually decreased in number and size after 30 days of age. Only a few small inclusions were seen in rats of 35 days of age or older, in spite of continuous injection of the drug.
Inclusions gradually decreased in number after discontinuation of the drug in a relatively younger age group. Injection of the drug in adult rats produced only a few small neuronal inclusions. Ultrastructurally, concentrical lamellar structures were the predominant ones in younger age groups but other types of inclusions were seen in older animals and those receiving lesser amounts of the drug or those which were examined after discontinuation of the drug. This observation suggests that morphologically different inclusions can be formed by basically the same treatment if there is any difference in the metabolic activity of the target cell or the amounts of the drug.
Biochemical analysis of the sterols revealed a consistently high level of 7-dehydrocholesterol up to 69 days of age, when AY9944 was administered continuously, despite the fact that there was a decrease in the number and size of the abnormal neuronal inclusions.
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Suzuki, K., Zagoren, J.C., Gonates, J. et al. Ultrastructural study of neuronal cytoplasmic inclusions produced by hypocholesterolemic Drug, AY 9944. Acta Neuropathol 26, 185–197 (1973). https://doi.org/10.1007/BF00684428
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DOI: https://doi.org/10.1007/BF00684428