Preferential regeneration and collateral dynamics of motor and sensory neurons after nerve injury in mice
Preferential regeneration and collateral dynamics of motor and sensory neurons after nerve injury in mice
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DOI：
10.1016/j.expneurol.2022.114227
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发表时间：
2022-09-21
影响因子：
5.3
通讯作者：
Udina，Esther
中科院分区：
文献类型：
--
作者：
Bolivar，Sara;Udina，Esther
周围神经损伤后再生的特异性是功能恢复的主要决定因素。不幸的是，再生的运动和感觉轴突很少找到它们原来的通路来重新支配适当的靶器官。虽然已经描述了运动轴突朝向肌肉再生的偏好，但对异质感觉群体的特异性知之甚少。在这里，我们建议在不同的神经元亚型的再生的比较研究。使用雌性和雄性报告小鼠，我们评估了运动神经元（ChAT-Cre/Ai 9），本体感受器（PV-Cre/Ai 9）和皮肤机械感受器（Npy 2 r-Cre/Ai 9）的再生偏好。这些动物的股神经在分叉处上方横断，并用纤维蛋白胶修复。在损伤后1或8周，通过在神经的远端分支中应用逆行示踪剂并计数分支中的逆行体和轴突来评估再生。我们发现，皮肤机械感受器再生速度比其他人群，其次是运动神经元，最后，本体感受器。所有类型的神经元有一个早期的偏好再生到皮肤分支，而在长期，所有的神经元再生更多的通过其原来的分支。最后，我们发现有髓鞘神经元在皮肤中比在股神经的肌肉分支中延伸出更多的再生芽，特别是运动神经元比本体感受器有更多的侧支。我们的研究结果揭示了再生动力学和特异性的新差异，这表明神经元亚型之间存在不同的再生机制，这些机制可能被调节以改善神经损伤后的功能恢复。
Specificity in regeneration after peripheral nerve injuries is a major determinant of functional recovery. Unfortunately, regenerating motor and sensory axons rarely find their original pathways to reinnervate appropriate target organs. Although a preference of motor axons to regenerate towards the muscle has been described, little is known about the specificity of the heterogeneous sensory populations. Here, we propose the comparative study of regeneration in different neuron subtypes. Using female and male reporter mice, we assessed the regenerative preference of motoneurons (ChAT-Cre/Ai9), proprioceptors (PV-Cre/Ai9), and cutaneous mechanoreceptors (Npy2r-Cre/Ai9). The femoral nerve of these animals was transected above the bifurcation and repaired with fibrin glue. Regeneration was assessed by applying retrograde tracers in the distal branches of the nerve 1 or 8 weeks after the lesion and counting the retrotraced somas and the axons in the branches. We found that cutaneous mechanoreceptors regenerated faster than other populations, followed by motoneurons and, lastly, proprioceptors. All neuron types had an early preference to regenerate into the cutaneous branch whereas, at long term, all neurons regenerated more through their original branch. Finally, we found that myelinated neurons extend more regenerative sprouts in the cutaneous than in the muscle branch of the femoral nerve and, particularly, that motoneurons have more collaterals than proprioceptors. Our findings reveal novel differences in regeneration dynamics and specificity, which indicate distinct regenerative mechanisms between neuron subtypes that can be potentially modulated to improve functional recovery after nerve injury.