Abstract：
We used α-Latrotoxin (α-LTx), the main neurotoxic component of the black widow spider venom, which causes degeneration of the neuromuscular junction (NMJ) followed by a rapid and complete regeneration, as a molecular tool to identify by RNA transcriptomics factors contributing to the structural and functional recovery of the NMJ. We found that Urocortin 2 (UCN2), a neuropeptide involved in the stress response, is rapidly expressed at the NMJ after acute damage and that inhibition of CRHR2, the specific receptor of UCN2, delays neuromuscular transmission rescue. Experiments in neuronal cultures show that CRHR2 localises at the axonal tips of growing spinal motor neurons and that its expression inversely correlates with synaptic maturation. Moreover, exogenous UCN2 enhances the growth of axonal sprouts in cultured neurons in a CRHR2-dependent manner, pointing to a role of the UCN2-CRHR2 axis in the regulation of axonal growth and synaptogenesis. Consistently, exogenous administration of UCN2 strongly accelerates the regrowth of motor axon terminals degenerated by α-LTx, thereby contributing to the functional recovery of neuromuscular transmission after damage. Taken together, our results posit a novel role for UCN2 and CRHR2 as a signalling axis involved in NMJ regeneration.
摘要：
我们使用了α-Latrotoxin(α-LTx),黑寡妇蜘蛛毒液的主要神经毒性成分，导致神经肌肉接头（NMJ）退化，然后快速完全再生，作为通过RNA转录组学鉴定有助于NMJ结构和功能恢复的因素的分子工具。我们发现Urocortin2（UCN2），一种参与应激反应的神经肽，急性损伤后在NMJ迅速表达，UCN2的特异性受体CRHR2的抑制延迟了神经肌肉传递的挽救。神经元培养物的实验表明，CRHR2位于生长中的脊髓运动神经元的轴突尖端，其表达与突触成熟成反比。此外，外源UCN2以CRHR2依赖性方式增强培养神经元中轴突芽的生长，指出UCN2-CRHR2轴在调节轴突生长和突触形成中的作用。始终如一，UCN2的外源给药强烈加速了α-LTx退化的运动轴突末端的再生，从而有助于损伤后神经肌肉传递的功能恢复。一起来看,我们的结果为UCN2和CRHR2作为参与NMJ再生的信号轴提供了新的作用。
