Moldovan Mihai, Rosberg Mette Romer, Alvarez Susana, Klein Dennis, Martini Rudolf, Krarup Christian
Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Neurophysiology, Rigshospitalet, Copenhagen, Denmark.
Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Neurobiol Aging. 2016 Mar;39:128-39. doi: 10.1016/j.neurobiolaging.2015.12.005. Epub 2015 Dec 18.
Accumulating myelin abnormalities and conduction slowing occur in peripheral nerves during aging. In mice deficient of myelin protein P0, severe peripheral nervous system myelin damage is associated with ectopic expression of Nav1.8 voltage-gated Na(+) channels on motor axons aggravating the functional impairment. The aim of the present study was to investigate the effect of regular aging on motor axon function with particular emphasis on Nav1.8. We compared tibial nerve conduction and excitability measures by threshold tracking in 12 months (mature) and 20 months (aged) wild-type (WT) mice. With aging, deviations during threshold electrotonus were attenuated and the resting current-threshold slope and early refractoriness were increased. Modeling indicated that, in addition to changes in passive membrane properties, motor fibers in aged WT mice were depolarized. An increased Nav1.8 isoform expression was found by immunohistochemistry. The depolarizing excitability features were absent in Nav1.8 null mice, and they were counteracted in WT mice by a Nav1.8 blocker. Our data suggest that alteration in voltage-gated Na(+) channel isoform expression contributes to changes in motor axon function during aging.
衰老过程中，周围神经会出现髓鞘异常累积和传导减慢的情况。在髓鞘蛋白P0缺乏的小鼠中，严重的周围神经系统髓鞘损伤与运动轴突上Nav1.8电压门控钠通道的异位表达有关，这会加重功能损害。本研究的目的是研究正常衰老对运动轴突功能的影响，特别关注Nav1.8。我们通过阈值跟踪比较了12个月（成熟）和20个月（老龄）野生型（WT）小鼠的胫神经传导和兴奋性指标。随着衰老，阈下电紧张期间的偏差减小，静息电流-阈值斜率和早期不应期增加。模型显示，除了被动膜特性的变化外，老龄WT小鼠的运动纤维发生了去极化。免疫组化发现Nav1.8亚型表达增加。Nav1.8基因敲除小鼠不存在去极化兴奋性特征，而WT小鼠中的这些特征可被Nav1.8阻滞剂抵消。我们的数据表明，电压门控钠通道亚型表达的改变有助于衰老过程中运动轴突功能的变化。
