聚焦离子束扫描电子显微镜将病理性髓鞘外翻与缺乏 Plp1 或 Mag 的小鼠的轴突变化联系起来,Glia

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聚焦离子束扫描电子显微镜将病理性髓鞘外翻与缺乏 Plp1 或 Mag 的小鼠的轴突变化联系起来
Glia ( IF 5.4 ) Pub Date : 2022-11-10 , DOI: 10.1002/glia.24290
Anna M Steyer _{1,

2} , Tobias J Buscham ₁ , Charlotta Lorenz ₃ , Sophie Hümmert ₁ , Maria A Eichel-Vogel ₁ , Leonie C Schadt ₁ , Julia M Edgar _{1,

4} , Sarah Köster _{3,

5} , Wiebke Möbius _{1,

2,

5} , Klaus-Armin Nave ₁ , Hauke B Werner ₁

Affiliation

健康的髓鞘由多个致密的膜层组成，紧密包裹着下面的轴突。CNS 髓鞘的超微结构需要专门的结构髓鞘蛋白，包括跨膜四跨蛋白脂质蛋白 (PLP) 和 Ig-CAM 髓鞘相关糖蛋白 (MAG)。为了更好地理解它们的功能相关性，我们询问了如果缺乏 PLP 或 MAG，轴突/髓鞘单位在多大程度上显示出相似的形态变化。因此，我们使用聚焦离子束扫描电子显微镜 (FIB-SEM) 并排重新研究Plp和Mag中的轴突/髓磷脂单元-无效突变小鼠。通过三维重建和形态测量分析，病理性髓鞘外翻在两种模型中沿着有髓轴突纵向延伸达 10 μm。超过一半的评估外流出现在节间髓鞘中。出乎意料的是，三维重建表明这两种模型都在髓鞘外翻下显示出复杂的轴突病理，包括轴突萌芽。在Plp中还观察到轴突吻合-无效突变小鼠。重要的是，根据电子显微照片的定量评估，正常出现的轴突/髓鞘单位在两种模型中都显示出显着增加的轴突直径。这些结果表明，健康的 CNS 髓鞘促进了正常的轴突直径和形状，当缺乏结构性髓鞘蛋白 PLP 或 MAG 时，该功能就会受损。

"点击查看英文标题和摘要"

Focused ion beam-scanning electron microscopy links pathological myelin outfoldings to axonal changes in mice lacking Plp1 or Mag

Healthy myelin sheaths consist of multiple compacted membrane layers closely encasing the underlying axon. The ultrastructure of CNS myelin requires specialized structural myelin proteins, including the transmembrane-tetraspan proteolipid protein (PLP) and the Ig-CAM myelin-associated glycoprotein (MAG). To better understand their functional relevance, we asked to what extent the axon/myelin-units display similar morphological changes if PLP or MAG are lacking. We thus used focused ion beam-scanning electron microscopy (FIB-SEM) to re-investigate axon/myelin-units side-by-side in Plp- and Mag-null mutant mice. By three-dimensional reconstruction and morphometric analyses, pathological myelin outfoldings extend up to 10 μm longitudinally along myelinated axons in both models. More than half of all assessed outfoldings emerge from internodal myelin. Unexpectedly, three-dimensional reconstructions demonstrated that both models displayed complex axonal pathology underneath the myelin outfoldings, including axonal sprouting. Axonal anastomosing was additionally observed in Plp-null mutant mice. Importantly, normal-appearing axon/myelin-units displayed significantly increased axonal diameters in both models according to quantitative assessment of electron micrographs. These results imply that healthy CNS myelin sheaths facilitate normal axonal diameters and shape, a function that is impaired when structural myelin proteins PLP or MAG are lacking.

更新日期：2022-11-10

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