Age-Dependent Schwann Cell Phenotype Regulation Following Peripheral Nerve Injury
Age-Dependent Schwann Cell Phenotype Regulation Following Peripheral Nerve Injury
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DOI：
10.1142/s0218810417500514
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发表时间：
2017-12-01
影响因子：
0.5
通讯作者：
Li, Zhongyu
中科院分区：
文献类型：
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作者：
Chen, Wayne A.;Luo, T. David;Li, Zhongyu
背景：雪旺细胞是周围神经系统再生能力的组成部分，青春期后神经系统的再生能力下降。这种衰退背后的机制尚不清楚。本研究旨在比较青春期和年轻成年大鼠神经挤压损伤后Notch、c-Jun和Krox-20的蛋白表达。我们假设这些雪旺细胞髓鞘调节因子在神经损伤后以年龄依赖性的方式下调。方法：选取青春期（2月龄）和青壮年（12月龄）大鼠48只进行坐骨神经挤压损伤。Western blot分析损伤后1、3、7 d Notch、c-Jun和Krox-20蛋白的表达。在另一组动物（n = 8）中，通过步态分析（坐骨功能指数）和肌电图（复合运动动作电位）评估损伤后8周的功能恢复情况。结果：青壮年大鼠的去分化调节因子Notch和c-Jun的出现有延迟的趋势，与青壮年大鼠的功能恢复相比，青壮年大鼠出现了延迟。青少年期大鼠复合动作电位面积明显大于青年期大鼠，幅度和速度均有统计学意义。结论：周围神经损伤后雪旺细胞脱分化过程随年龄的增长有不同的变化趋势。这些导致雪旺细胞髓鞘形成的关键调控因子延迟发生的趋势可能是导致青少年和年轻成年大鼠周围神经损伤后功能恢复显著差异的众多可能因素之一。
Background: Schwann cells are integral to the regenerative capacity of the peripheral nervous system, which declines after adolescence. The mechanisms underlying this decline are poorly understood. This study sought to compare the protein expression of Notch, c-Jun, and Krox-20 after nerve crush injury in adolescent and young adult rats. We hypothesized that these Schwann cell myelinating regulatory factors are down-regulated after nerve injury in an age-dependent fashion.Methods: Adolescent (2 months old) and young adult (12 months old) rats (n = 48) underwent sciatic nerve crush injury. Protein expression of Notch, c-Jun, and Krox-20 was quantified by Western blot analysis at 1, 3, and 7 days post-injury. Functional recovery was assessed in a separate group of animals (n = 8) by gait analysis (sciatic functional index) and electromyography (compound motor action potential) over an 8-week post-injury period.Results: Young adult rats demonstrated a trend of delayed onset of the dedifferentiating regulatory factors, Notch and c-Jun, corresponding to the delayed functional recovery observed in young adult rats compared to adolescent rats. Compound motor action potential area was significantly greater in adolescent rats relative to young adult rats, while amplitude and velocity trended toward statistical significance.Conclusions: The process of Schwann cell dedifferentiation following peripheral nerve injury shows different trends with age. These trends of delayed onset of key regulatory factors responsible for Schwann cell myelination may be one of many possible factors mediating the significant differences in functional recovery between adolescent and young adult rats following peripheral nerve injury.