Decreased number and increased volume with mitochondrial enlargement of cerebellar synaptic terminals in a mouse model of chronic demyelination
Decreased number and increased volume with mitochondrial enlargement of cerebellar synaptic terminals in a mouse model of chronic demyelination
复制标题
慢性脱髓鞘小鼠模型中小脑突触末端线粒体增大导致数量减少和体积增加
DOI：
10.1007/s00795-018-0193-z
复制
发表时间：
2018
影响因子：
1.8
通讯作者：
Ohno Nobuhiko
中科院分区：
文献类型：
--
作者：
Nguyen Huy Bang;Sui Yang;Thai Truc Quynh;Ikenaka Kazuhiro;Oda Toshiyuki;Ohno Nobuhiko
神经传导受损，轴突变性和突触改变有助于炎性脱髓鞘疾病的神经功能障碍。小脑功能障碍与脱髓鞘疾病有关，但慢性脱髓鞘过程中小脑灰质轴突终末的改变尚不清楚。我们分析了遗传性慢性脱髓鞘小鼠模型攀爬纤维末端的形态和超微结构变化。在髓鞘基因（PLP4e）额外拷贝引起的脱髓鞘小鼠模型中，使用连续块面扫描电镜和突触标记物免疫染色进行三维超微结构分析。在1月龄时，PLP4e和野生型小鼠中观察到许多髓鞘轴突，但在5月龄时，PLP4e小鼠中脱髓鞘轴突和髓鞘异常薄的轴突突出。PLP4e小鼠在5月龄时攀爬纤维终端密度显著降低。攀爬纤维末端重建显示，PLP4e攀爬纤维在5月龄小鼠的静脉曲张中增加了体积，线粒体增大。这些结果表明，慢性脱髓鞘与小脑皮层攀爬纤维末端的改变和丧失有关，并且突触的改变可能有助于在遗传性脱髓鞘疾病中观察到的小脑表型。
Impaired nerve conduction, axonal degeneration, and synaptic alterations contribute to neurological disabilities in inflammatory demyelinating diseases. Cerebellar dysfunction is associated with demyelinating disorders, but the alterations of axon terminals in cerebellar gray matter during chronic demyelination are still unclear. We analyzed the morphological and ultrastructural changes of climbing fiber terminals in a mouse model of hereditary chronic demyelination. Three-dimensional ultrastructural analyses using serial block-face scanning electron microscopy and immunostaining for synaptic markers were performed in a demyelination mouse model caused by extra copies of myelin gene (PLP4e). At 1 month old, many myelinated axons were observed in PLP4e and wild-type mice, but demyelinated axons and axons with abnormally thin myelin were prominent in PLP4e mice at 5 months old. The density of climbing fiber terminals was significantly reduced in PLP4e mice at 5 months old. Reconstruction of climbing fiber terminals revealed that PLP4e climbing fibers had increased varicosity volume and enlarged mitochondria in the varicosities at 5-month-old mice. These results suggest that chronic demyelination is associated with alterations and loss of climbing fiber terminals in the cerebellar cortex, and that synaptic changes may contribute to cerebellar phenotypes observed in hereditary demyelinating disorders.