Wallerian Degeneration: A Major Component of Early Axonal Pathology in Multiple Sclerosis
Wallerian Degeneration: A Major Component of Early Axonal Pathology in Multiple Sclerosis
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DOI：
10.1111/j.1750-3639.2010.00401.x
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发表时间：
2010-09-01
期刊：
影响因子：
6.4
通讯作者：
Brueck, Wolfgang
中科院分区：
文献类型：
--
作者：
Dziedzic, Tomasz;Metz, Imke;Brueck, Wolfgang
轴突缺失是多发性硬化（MS）病理学的主要组成部分，也是永久性临床残疾的形态学基础。它发生在脱髓鞘斑块中，但也发生在所谓的正常外观白色物质（NAWM）中。然而，沃勒变性对轴突病理的贡献尚不清楚。在这里，我们分析了63例多发性硬化患者早期多发性硬化活检组织中斑块周围白色物质（PPWM）和病变的沃勒变性和轴突病理的程度。使用抗神经肽Y受体Y1（NPY-Y1 R）的抗体观察沃勒变性。与对照白色物质相比，PPWM和斑块中具有非磷酸化神经丝的SMI-32阳性轴突的数量显著较高。APP阳性，急性损伤的轴突被发现在斑块中的显着较高的数字相比，PPWM。值得注意的是，在PPWM和斑块中发生沃勒变性的NPY-Y1 R阳性轴突的数量显著高于对照WM。PPWM中的NPY-Y1 R阳性轴突与病变中的NPY-Y1 R阳性轴突密切相关。我们的研究结果表明，华勒变性是一个主要组成部分的轴突病理在斑块周围的白色物质在早期MS。它可能有助于在早期MS中观察到的放射性变化，最有可能发挥了重要作用的残疾的发展。
Axonal loss is a major component of the pathology of multiple sclerosis (MS) and the morphological basis of permanent clinical disability. It occurs in demyelinating plaques but also in the so-called normal-appearing white matter (NAWM). However, the contribution of Wallerian degeneration to axonal pathology is not known. Here, we analyzed the extent of Wallerian degeneration and axonal pathology in periplaque white matter (PPWM) and lesions in early multiple sclerosis biopsy tissue from 63 MS patients. Wallerian degeneration was visualized using an antibody against the neuropeptide Y receptor Y1 (NPY-Y1R). The number of SMI-32-positive axons with non-phosphorylated neurofilaments was significantly higher in both PPWM and plaques compared to control white matter. APP-positive, acutely damaged axons were found in significantly higher numbers in plaques compared to PPWM. Strikingly, the number of NPY-Y1R-positive axons undergoing Wallerian degeneration was significantly higher in PPWM and plaques than in control WM. NPY-Y1R-positive axons in PPWM were strongly correlated to those in the lesions. Our results show that Wallerian degeneration is a major component of axonal pathology in the periplaque white matter in early MS. It may contribute to radiological changes observed in early MS and most likely plays a major role in the development of disability.