Altered terminal Schwann cell morphology precedes denervation in SOD1 mice.
Altered terminal Schwann cell morphology precedes denervation in SOD1 mice.
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DOI：
10.1016/j.expneurol.2015.09.014
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发表时间：
2016-01
影响因子：
5.3
通讯作者：
Pinter MJ
中科院分区：
文献类型：
--
作者：
Carrasco DI;Seburn KL;Pinter MJ
在表达在人类运动神经元疾病中发现的SOD1突变的小鼠中，变性开始于外周，原因尚不清楚。在神经肌肉接头（NMJ），终末雪旺细胞（TSC）与运动终末有着密切的关系，并被认为有助于维持运动终末的完整性。最近的证据表明，在一些SOD1小鼠的TSC表现出异常的功能特性，但可能的TSC参与的其他方面仍然未知。在这项研究中，在表达G93A SOD1突变的小鼠中，对TSC形态和数量与NMJ神经支配状态进行了分析。在P30，所有的NMJ的快内侧腓肠肌（MG）肌肉完全由一个单一的运动轴突，但50%的NMJ缺乏TSC细胞体，而是覆盖的雪旺细胞的细胞体位于前终末轴突的过程。P30慢比目鱼肌中的NMJ也完全由单个运动轴突支配，只有5%的NMJ缺乏TSC细胞体。在P60时，约25%的MG NMJ失神经支配并且缺乏TSC标记，而约60%的神经支配的NMJ缺乏TSC细胞体。相反，96%的P60比目鱼肌NMJ受神经支配，而9%的受神经支配的NMJ缺乏TSC细胞体。因此，在P30发现的TSC异常模式与在P60发现的去神经支配模式相关。来自表达G85R SOD1突变的小鼠的证据表明，TSC异常对于表达G93A SOD1突变的小鼠并不独特。这些结果增加了一个新兴的理解，即在运动神经元疾病的动物模型中，TSC可能在运动终末变性和去神经支配中发挥作用。
In mice that express SOD1 mutations found in human motor neuron disease, degeneration begins in the periphery for reasons that remain unknown. At the neuromuscular junction (NMJ), terminal Schwann cells (TSCs) have an intimate relationship with motor terminals and are believed to help maintain the integrity of the motor terminal. Recent evidence indicates that TSCs in some SOD1 mice exhibit abnormal functional properties, but other aspects of possible TSC involvement remain unknown. In this study, an analysis of TSC morphology and number was performed in relation to NMJ innervation status in mice which express the G93A SOD1 mutation. At P30, all NMJs of the fast medial gastrocnemius (MG) muscle were fully innervated by a single motor axon but 50% of NMJs lacked TSC cell bodies and were instead covered by the processes of Schwann cells with cell bodies located on the preterminal axons. NMJs in P30 slow soleus muscles were also fully innervated by single motor axons and only 5% of NMJs lacked a TSC cell body. At P60, about 25% of MG NMJs were denervated and lacked labeling for TSCs while about 60% of innervated NMJs lacked TSC cell bodies. In contrast, 96% of P60 soleus NMJs were innervated while 9% of innervated NMJs lacked TSC cell bodies. The pattern of TSC abnormalities found at P30 thus correlates with the pattern of denervation found at P60. Evidence from mice that express the G85R SOD1 mutation indicate that TSC abnormalities are not unique for mice that express G93A SOD1 mutations. These results add to an emerging understanding that TSCs may play a role in motor terminal degeneration and denervation in animal models of motor neuron disease.