Remyelination after cuprizone-induced demyelination in the rat is stimulated by apotransferrin
Remyelination after cuprizone-induced demyelination in the rat is stimulated by apotransferrin
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DOI：
10.1016/j.expneurol.2005.12.027
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发表时间：
2006-04-01
影响因子：
5.3
通讯作者：
Soto, EF
中科院分区：
文献类型：
--
作者：
Adamo, AM;Paez, PM;Soto, EF
21日龄Wistar大鼠饲喂含0.6%铜的饲料2周。停药后所进行的研究显示，胼胝体有明显的脱髓鞘组织学证据。对分离的髓鞘的生化研究表明，髓鞘蛋白、磷脂和半乳脑苷脂显著减少，髓鞘产量显著减少。通过组织学、免疫细胞化学和生化参数的评估，这些动物在停药时一次脑内注射350 ng的载脂蛋白可显著增加髓鞘沉积，从而显著改善再髓鞘形成，与自发恢复时观察到的情况相比。冰冻切片免疫细胞化学研究分析了停药时及以后不同时间少突胶质细胞群的发育参数。结果显示，在未处理的动物中，NG2-BrdU阳性的前体细胞数量显著增加，而在铜酮诱导的脱髓鞘高峰期，MBP的表达显著降低。正如预期的那样，在自发的再髓鞘形成过程中，前体细胞的数量显著减少，并伴随着MBP反应性的增加。在用载脂转铁蛋白处理的动物中，这些现象发生得更快，再髓鞘形成的效率也比未处理的对照组高得多，本研究结果表明，载脂转铁蛋白是一种非常活跃的早髓鞘因子，对某些脱髓鞘疾病的治疗可能是重要的。(C)2006 Elsevier Inc.保留所有权利。
Twenty-one-day-old Wistar rats were fed a diet containing 0.6% cuprizone for 2 weeks. Studies carried out after withdrawal of cuprizone showed histological evidences of marked demyelination in the corpus callosum. Biochemical Studies of isolated myelin showed a marked decrease in myelin proteins, phospholipids, and galactocerebrosides as well as a marked decrease in myelin yield. Treatment of these animals with a single intracranial injection of 350 ng of apotransferrin at the time of withdrawal of cuprizone induced a marked increase in myelin deposition resulting in a significantly improved remyelination, evaluated by histological, immunocytochemical, and biochemical parameters, in comparison to what was observed in spontaneous recovery. Immunocytochemical studies of cryotome sections to analyze developmental parameters of the oligodendroglial cell population at the time of termination of cuprizone and at different times thereafter showed that in the untreated animals, there was a marked increase in the number of NG2-BrdU-positive precursor cells together with a marked decrease in MBP expression at the peak of cuprizone-induced demyelination. As expected, the amount of precursor cells decreased markedly during spontaneous remyelination and was accompanied by an increase in MBP reactivity. In the apotransferrin-treated animals, these phenomena occurred much faster, and remyelination was much more efficient than in the untreated controls, The results of this study suggest that apotransferrin is a very active promyelinating agent which could be important for the treatment of certain demyelinating conditions. (C) 2006 Elsevier Inc. All rights reserved.