Long-term analyses of innervation and neuromuscular integrity in the Trembler-J mouse model of Charcot-Marie-Tooth disease.
Long-term analyses of innervation and neuromuscular integrity in the Trembler-J mouse model of Charcot-Marie-Tooth disease.
复制标题
对腓骨肌萎缩症 Trembler-J 小鼠模型的神经支配和神经肌肉完整性进行长期分析。
DOI：
10.1097/nen.0b013e3182a5f96e
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发表时间：
2013
影响因子：
3.2
通讯作者：
Notterpek,Lucia
中科院分区：
文献类型：
--
作者：
Nicks,JessicaRenee;Lee,Sooyeon;Kostamo,KathryneAnn;Harris,AndrewBenford;Sookdeo,AmandaM;Notterpek,Lucia
大部分遗传性脱髓鞘性神经病，归类为腓骨肌萎缩症1A型，与外周髓鞘蛋白22的错误表达有关。在这项研究中，我们的特点是发生在Trembler-J小鼠，Charcot-Marie-Tooth病1A型的自发啮齿动物模型的神经肌肉组织中的疾病进展的形态学和生化变化。使用年龄匹配的2个月和10个月大的野生型和Trembler-J小鼠，我们观察到从远端到近端区域的神经肌肉缺陷。运动表现的损伤通过远端神经节段的退行性事件和神经-肌肉突触的结构改变来强调。此外，受影响小鼠的骨骼肌显示肌纤维直径减小，肌肉萎缩标志物肌肉环指蛋白1的表达增加，以及纤维类型转换。间歇性禁食的饮食干预减弱了这些进行性变化，并支持远端神经髓鞘形成和神经肌肉接头的完整性。除了该模型的良好表征的脱髓鞘方面之外，我们的研究还确定了受影响的神经病小鼠的远端神经和肌肉中的不同退行性事件。因此，旨在减缓或逆转这些疾病的神经病变特征的治疗研究应包括肌肉组织以及神经肌肉接触部位的检查。
A large fraction of hereditary demyelinating neuropathies, classified as Charcot-Marie-Tooth disease type 1A, is associated with misexpression of peripheral myelin protein 22. In this study, we characterized morphologic and biochemical changes that occur with disease progression in neuromuscular tissue of Trembler-J mice, a spontaneous rodent model of Charcot-Marie-Tooth disease type 1A. Using age-matched, 2- and 10-month-old, wild-type and Trembler-J mice, we observed neuromuscular deficits that progress from distal to proximal regions. The impairments in motor performance are underlined by degenerative events at distal nerve segments and structural alterations at nerve-muscle synapses. Furthermore, skeletal muscle of affected mice showed reduced myofiber diameter, increased expression of the muscle atrophy marker muscle ring-finger protein 1, and fiber type switching. A dietary intervention of intermittent fasting attenuated these progressive changes and supported distal nerve myelination and neuromuscular junction integrity. In addition to the well-characterized demyelination aspects of this model, our investigations identified distinct degenerative events in distal nerves and muscle of affected neuropathic mice. Therefore, therapeutic studies aimed at slowing or reversing the neuropathic features of these disorders should include the examination of muscle tissue, as well as neuromuscular contact sites.