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  • 1
    ISSN: 1432-0533
    Keywords: Neuronal Inclusions ; Cerebrum ; Cholesterol Inhibitor ; Rat ; Electron Microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0533
    Keywords: Cholesterol Inhibitors ; Cerebrum ; Neuronal Inclusions ; Oligodendroglial Degeneration ; Rat ; Abnormal Sterols
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Wistar strain of rats received daily intraperitoneal or oral administration of Triparanol, 250 mg per kg of body weight or 20,25-diazacholesterol either 30 mg or 60 mg per kg of body weight starting at the age of 5 days old. Prominent intracytoplasmic osmiophilic inclusions identical to those found in the rats treated with AY9944 (Suzukiet al., 1973) and degeneration of myelin sheaths and oligodendroglia were seen in the myelinating white matter of rats sacrificed after 3, 6, and 9 injections of Triparanol. In diazacholesterol-treated animals, a few identical inclusions were seen in the cortical neurons but only slight changes were seen in oligodendroglia. Biochemical analysis of the brains of the rats receiving Triparanol revealed a large accumulation ofΔ 7,24-cholestadiene-3β-ol and lesser amounts of desmosterol. The brains of the animals treated with diazacholesterol revealed massive accumulation of desmosterol and a minor sterol component, probablyΔ 5,7,24-cholestatriene-3β-ol. Since AY9944, which results in a massive accumulation of 7 dehydrocholesterol (Δ 5,7-cholestadiene-3β-ol) and two other sterols,Δ 7,24-cholestadiene-3β-ol andΔ 5,7,24-cholestatriene-3β-ol, will produce identical neuropathological lesions to those seen in Triparanol treated animals, and since the lesion produced in diazacholesterol treated animals was very slight, there appears to be a correlation between the presence of sterols with a double bond at the 7-position and neuropathological lesions in young rats.
    Type of Medium: Electronic Resource
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