Norkute Akvile, Hieble Andrea, Braun Alena, Johann Sonja, Clarner Tim, Baumgartner Werner, Beyer Cordian, Kipp Markus
Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.
J Neurosci Res. 2009 May 1;87(6):1343-55. doi: 10.1002/jnr.21946.
Memory impairment is outstanding within the spectrum of cognitive deficits in multiple sclerosis (MS) patients. Demyelination has been reported in the hippocampus formation of MS patients. The degree of hippocampus lesions in MS strongly correlates with progression of cognitive dysfunction. Because no appropriate animal model for the study of hippocampus demyelination has been established, we used the cuprizone mouse model to investigated demyelination in young adult and aged mice. The myelin status was analyzed by classical histological staining, immunocytochemistry for proteolipoprotein, and electron microscopy. Oligodendrocyte, astroglial, and microglia markers were studied. Cuprizone intoxication induced an almost complete demyelination of distinct hippocampus subregions to a similar extent in young adult and aged male mice. Demyelination was pronounced in a subset of white and gray matter areas, i.e., the stratum lacunosum moleculare containing the perforant path, medial alveus, stratum pyramidale in the cornu ammonis 2/3 region, and hilus region. Besides demyelination, affected areas displayed hypertrophic and hyperplastic astrocytosis. No significant effect on microglia invasion was detected at any investigated time point (0, 3, 5, and 7 weeks). We conclude that cuprizone-induced demyelination provides an adequate animal model to investigate appropriate therapy strategies for the prevention of hippocampus demyelination.
在多发性硬化症（MS）患者的认知缺陷范围内，记忆障碍较为突出。已有报道称MS患者的海马结构存在脱髓鞘现象。MS中海马病变的程度与认知功能障碍的进展密切相关。由于尚未建立用于研究海马脱髓鞘的合适动物模型，我们使用铜螯合剂诱导的小鼠模型来研究年轻成年小鼠和老年小鼠的脱髓鞘情况。通过经典组织学染色、蛋白脂蛋白免疫细胞化学和电子显微镜分析髓鞘状态。研究了少突胶质细胞、星形胶质细胞和小胶质细胞标志物。铜螯合剂中毒在年轻成年雄性小鼠和老年雄性小鼠中诱导不同海马亚区域几乎完全脱髓鞘，程度相似。脱髓鞘在白质和灰质区域的一个子集中较为明显，即包含穿通通路的分子层、内侧齿状回、海马2/3区的锥体层和海马 hilus 区。除了脱髓鞘，受影响区域还表现出肥大和增生性星形胶质细胞增多。在任何研究时间点（0、3、5和7周）均未检测到对小胶质细胞浸润的显著影响。我们得出结论，铜螯合剂诱导的脱髓鞘为研究预防海马脱髓鞘的合适治疗策略提供了一个合适的动物模型。
