The long-term sequelae of nerve injury as well as age-related neurodegeneration have been documented in numerous studies, however the role of Cx32 in these processes is not well understood. There is a need for better understanding of the molecular mechanisms that underlie long-term suboptimal nerve function and for approaches to prevent or improve it. In this communication we describe our studies using whole animal electrophysiology to examine the long-term sequelae of sciatic nerve crush in both WT and Cx32KO mice, a model of X-linked Charcot Marie Tooth disease, a subtype of inherited peripheral neuropathies. We present results from electrical nerve recordings done 14 to 27 days and 18 to 20 months after a unilateral sciatic nerve crush performed on 35 to 37-day old mice. Contrary to expectations, we find that whereas crush injury leads to a degradation of WT nerve function relative to uninjured nerves at 18 to 20 months, previously crushed Cx32KO nerves perform at the same level as their uninjured counterparts. Thus, 18 to 20 months after injury, WT nerves perform below the level of normal (uninjured) WT nerves in both motor and sensory nerve function. In contrast, measures of nerve function in Cx32KO mice are degraded for sensory axons but exhibit no additional dysfunction in motor axons. Early nerve injury has no negative electrophysiologic effect on the Cx32 KO motor nerves. Based on our prior demonstration that the transcriptomic profile of uninjured Cx32KO and injured WT sciatic nerves are very similar, the lack of an additional effect of crush on Cx32KO motor nerve parameters suggests that Cx32 knockout may implement a form of neuroprotection that limits the effects of subsequent injury.

中文翻译：

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早期挤压对衰老野生型和 Connexin 32 敲除小鼠的影响：CMT1X 小鼠神经神经保护状态的证据


大量研究已记录了神经损伤的长期后遗症以及与年龄相关的神经变性，但 Cx32 在这些过程中的作用尚不清楚。需要更好地了解神经功能长期欠佳的分子机制，并寻找预防或改善神经功能的方法。在本次通讯中，我们描述了我们的研究，使用整个动物电生理学来检查 WT 和 Cx32KO 小鼠坐骨神经挤压的长期后遗症，这是 X 连锁夏科玛丽图斯病（遗传性周围神经病的一种亚型）的模型。我们展示了对 35 至 37 天龄小鼠进行单侧坐骨神经挤压后 14 至 27 天和 18 至 20 个月进行的神经电记录结果。与预期相反，我们发现，虽然挤压损伤会导致 WT 神经功能在 18 至 20 个月时相对于未受伤的神经退化，但之前被挤压的 Cx32KO 神经的表现与未受伤的神经处于相同的水平。因此，受伤后 18 至 20 个月，WT 神经的运动和感觉神经功能均低于正常（未受伤）WT 神经的水平。相比之下，Cx32KO 小鼠的神经功能测量结果是感觉轴突退化，但运动轴突没有表现出额外的功能障碍。早期神经损伤对 Cx32 KO 运动神经没有负面的电生理影响。根据我们之前的证明，未受伤的 Cx32KO 和受伤的 WT 坐骨神经的转录组学特征非常相似，挤压对 Cx32KO 运动神经参数没有额外的影响，这表明 Cx32 敲除可能会实现一种神经保护形式，限制随后的影响。受伤。