Spinal axon regeneration induced by elevation of cyclic AMP
Spinal axon regeneration induced by elevation of cyclic AMP
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DOI：
10.1016/s0896-6273(02)00730-4
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发表时间：
2002-06-13
期刊：
影响因子：
16.2
通讯作者：
Filbin, MT
中科院分区：
文献类型：
--
作者：
Qiu, J;Cai, CM;Filbin, MT
髓鞘抑制剂，包括MAG，是CNS再生的主要障碍。然而，如果先损伤这些神经元的外周分支，则DRG的CNS轴突再生。我们发现外周损伤后1天，DRG-cAMP水平增加三倍，MAG/髓鞘不再抑制生长，这种作用是PKA依赖性的。到损伤后1周，DRG-cAMP恢复到对照，但MAG/髓磷脂上的生长改善并且现在是PKA独立的。在体内抑制PKA在1天阻断MAG/髓磷脂上的损伤后生长，并在1周时使其减弱。单独地，注射db-cAMP到DRG中完全模拟了条件性损伤，因为DRG最初以PKA依赖性方式在MAG/髓磷脂上生长，该PKA依赖性方式变为PKA独立性。重要的是，DRG注射db-cAMP导致1周后损伤的背柱轴突的广泛再生。这些结果可能与开发脊髓损伤的治疗方法有关。
Myelin inhibitors, including MAG, are major impediments to CNS regeneration. However, CNS axons of DRGs regenerate if the peripheral branch of these neurons is lesioned first. We show that 1 day post-peripheral-lesion, DRG-cAMP levels triple and MAG/myelin no longer inhibit growth, an effect that is PKA dependent. By 1 week post-lesion, DRG-cAMP returns to control, but growth on MAG/myelin improves and is now PKA independent. Inhibiting PKA in vivo blocks the post-lesion growth on MAG/myelin at 1 day and attenuates it at I week. Alone, injection of db-cAMP into the DRG mimics completely a conditioning lesion as DRGs grow on MAG/myelin, initially, in a PKA-dependent manner that becomes PKA independent. Importantly, DRG injection of db-cAMP results in extensive regeneration of dorsal column axons lesioned 1 week later. These results may be relevant to developing therapies for spinal cord injury.