Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen N, Denmark.
Neurochem Res. 2013 Jun;38(6):1266-77. doi: 10.1007/s11064-013-1030-3. Epub 2013 Apr 7.
Mice with a heterozygous knock-out of the myelin protein P0 gene (P0+/-) develop a neuropathy similar to human Charcot-Marie-Tooth disease. They are indistinguishable from wild-types (WT) at birth and develop a slowly progressing demyelinating neuropathy. The aim of this study was to investigate whether the regeneration capacity of early symptomatic P0+/- is impaired as compared to age matched WT. Right sciatic nerves were lesioned at the thigh in 7-8 months old mice. Tibial motor axons at ankle were investigated by conventional motor conduction studies and axon excitability studies using threshold tracking. To evaluate regeneration we monitored the recovery of motor function after crush, and then compared the fiber distribution by histology. The overall motor performance was investigated using Rotor-Rod. P0+/- had reduced compound motor action potential amplitudes and thinner myelinated axons with only a borderline impairment in conduction and Rotor-Rod. Plantar muscle reinnervation occurred within 21 days in all mice. Shortly after reinnervation the conduction of P0+/- regenerated axons was markedly slower than WT, however, this difference decayed with time. Nevertheless, after 1 month, regenerated P0+/- axons had longer strength-duration time constant, larger threshold changes during hyperpolarizing electrotonus and longer relative refractory period. Their performance at Rotor-Rod remained also markedly impaired. In contrast, the number and diameter distribution of regenerating myelinated fibers became similar to regenerated WT. Our data suggest that in the presence of heterozygously P0 deficient Schwann cells, regenerating motor axons retain their ability to reinnervate their targets and remyelinate, though their functional recovery is delayed.
杂合敲除髓鞘蛋白 P0 基因的小鼠（P0+/-）会发展出类似于人类夏科-马里-图什病的神经病。它们在出生时与野生型（WT） indistinguishable，并发展出缓慢进展的脱髓鞘神经病。本研究旨在研究与年龄匹配的 WT 相比，早期有症状的 P0+/- 的再生能力是否受损。在 7-8 个月大的小鼠的大腿处损伤右侧坐骨神经。通过常规运动传导研究和使用阈值跟踪的轴突兴奋性研究来研究踝部的胫骨运动轴突。为了评估再生，我们监测了挤压后运动功能的恢复情况，然后通过组织学比较纤维分布。使用旋转棒来评估整体运动性能。P0+/- 的复合运动动作电位幅度降低，有髓轴突较细，传导速度和旋转棒仅略有受损。所有小鼠的足底肌肉均在 21 天内重新支配。在重新支配后不久，P0+/- 再生轴突的传导速度明显慢于 WT，但随着时间的推移这种差异逐渐减弱。然而，在 1 个月后，再生的 P0+/- 轴突的强度-持续时间时间常数更长，超极化电紧张时的阈值变化更大，相对不应期更长。它们在旋转棒上的表现仍然明显受损。相比之下，再生有髓纤维的数量和直径分布变得与再生的 WT 相似。我们的数据表明，在杂合 P0 缺陷 Schwann 细胞存在的情况下，再生的运动轴突仍然能够重新支配其靶标并重新髓鞘化，尽管它们的功能恢复延迟了。
