CHANGES IN BRAIN HYDROLYTIC ENZYME-ACTIVITIES IN RATS TREATED WITH CHOLESTEROL-BIOSYNTHESIS INHIBITOR, AY9944
CHANGES IN BRAIN HYDROLYTIC ENZYME-ACTIVITIES IN RATS TREATED WITH CHOLESTEROL-BIOSYNTHESIS INHIBITOR, AY9944
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DOI：
10.1016/0006-8993(75)90685-x
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发表时间：
1975-01-01
期刊：
影响因子：
2.9
通讯作者：
SUZUKI, K
中科院分区：
文献类型：
--
作者：
IGARASHI, M;SUZUKI, K;SUZUKI, K
腹腔内给予 AY9944 会导致 7-脱氢胆固醇蓄积、含有酸性磷酸酶活性的异常神经元细胞质层状包涵体的出现以及少突胶质细胞的变性。在本研究中，我们试图将异常包涵体的出现和消失、少突胶质细胞变性、溶酶体酶的活性和 7-脱氢胆固醇的积累联系起来。一组 5 日龄大鼠每天注射 AY9944，剂量为 30 mg/kg，持续 30 天。其他组接受相同的每日剂量，但仅连续 10 天，分别从第 5、15、25 和 35 天开始。测定了 13 种脑水解酶的活性。在第一组中，大多数酶的活性比对照组有所增加，在第 15 天和第 25 天之间达到峰值，对应于神经元内含物和退化少突胶质细胞的最大程度出现。尽管继续施用 AY9944 且 7-脱氢胆固醇的组织浓度较高，但大多数酶的活性在 25 天后下降至相对稳定的水平，略高于对照。在接受10天注射的组中，酶活性在注射结束时达到峰值，然后在10天内迅速恢复正常，与异常包涵体的出现和消失相对应。但停药后10天内7-脱氢胆固醇继续升高。 AY9944 在体外对任何酶均没有直接影响。在实验条件下，似乎存在普遍的溶酶体激活伴随着异常神经元包涵体的形成。
Intraperitoneal administration of AY9944 causes accumulation of 7-dehydrocholesterol, appearance of abnormal neuronal cytoplasmic lamellar inclusions containing acid phosphatase activities, and degeneration of oligodendroglial cells. In the present study, we attempted to correlate appearance and disappearance of abnormal inclusions, oligodendroglial degeneration, activities of lysosomal enzymes, and accumulation of 7-dehydrocholesterol. One group of 5-day-old rats received daily injection of AY9944, 30 mg/kg, for 30 days. Other groups received the same daily dosage but only for 10 consecutive days, starting from 5, 15, 25, and 35 days, respectively. Activities of 13 brain hydrolytic enzymes were determined. In the first group, activities of most enzymes increased over the controls, reaching the peak between the 15th and 25th day, corresponding to the maximum appearance of the neuronal inclusions and degenerating oligodendroglia. Despite the continued administration of AY9944 and the high tissue concentration of 7-dehydrocholesterol, activities of most enzymes declined after 25 days to relatively steady levels somewhat higher than controls. In the group which received 10-day injections, enzyme activities reached the peak at the end of the injections and then rapidly returned to normal within 10 days thereafter, corresponding to the appearance and disappearance of the abnormal inclusions. However, 7-dehydrocholesterol continued to increased for 10 days after the drug administration was discontinued. AY9944 had no direct effect on any of the enzymesin vitro. There appears to be generalized lysosomal activation concomitant with formation of abnormal neuronal inclusions in the experimental conditions.