The Eugene Bell Center for Regenerative Biology and Tissue Engineering, Marine Biological Laboratory, Woods Hole, Massachusetts, United States of America.
PLoS One. 2019 Jan 30;14(1):e0204193. doi: 10.1371/journal.pone.0204193. eCollection 2019.
The resilience of regeneration in vertebrates is not very well understood. Yet understanding if tissues can regenerate after repeated insults, and identifying limitations, is important for elucidating the underlying mechanisms of tissue plasticity. This is particularly challenging in tissues, such as the nervous system, which possess a large number of terminally differentiated cells and often exhibit limited regeneration in the first place. However, unlike mammals, which exhibit very limited regeneration of spinal cord tissues, many non-mammalian vertebrates, including lampreys, bony fishes, amphibians, and reptiles, regenerate their spinal cords and functionally recover even after a complete spinal cord transection. It is well established that lampreys undergo full functional recovery of swimming behaviors after a single spinal cord transection, which is accompanied by tissue repair at the lesion site, as well as axon and synapse regeneration. Here we begin to explore the resilience of spinal cord regeneration in lampreys after a second spinal transection (re-transection). We report that by all functional and anatomical measures tested, lampreys regenerate after spinal re-transection just as robustly as after single transections. Recovery of swimming, synapse and cytoskeletal distributions, axon regeneration, and neuronal survival were nearly identical after spinal transection or re-transection. Only minor differences in tissue repair at the lesion site were observed in re-transected spinal cords. Thus, regenerative potential in the lamprey spinal cord is largely unaffected by spinal re-transection, indicating a greater persistent regenerative potential than exists in some other highly regenerative models. These findings establish a new path for uncovering pro-regenerative targets that could be deployed in non-regenerative conditions.
脊椎动物再生的弹性还不是很清楚。然而，了解组织在多次损伤后是否可以再生，并确定其局限性，对于阐明组织可塑性的潜在机制非常重要。这在神经系统等组织中尤其具有挑战性，这些组织具有大量终末分化的细胞，并且最初通常表现出有限的再生能力。然而，与表现出脊髓组织非常有限再生能力的哺乳动物不同，包括七鳃鳗、硬骨鱼、两栖动物和爬行动物在内的许多非哺乳动物脊椎动物会再生其脊髓，并在完全脊髓横断后恢复功能。已经证实，七鳃鳗在单次脊髓横断后会完全恢复游泳行为，伴随着损伤部位的组织修复，以及轴突和突触的再生。在这里，我们开始探索七鳃鳗在第二次脊髓横断（再横断）后的脊髓再生弹性。我们报告说，通过所有测试的功能和解剖学测量，七鳃鳗在再横断后再生与单次横断后一样强劲。游泳、突触和细胞骨架分布、轴突再生和神经元存活的恢复在脊髓横断或再横断后几乎完全相同。仅在再横断的脊髓中观察到损伤部位的组织修复有轻微差异。因此，七鳃鳗脊髓的再生潜力受脊髓再横断的影响不大，这表明其再生潜力比其他一些高度再生的模型更大。这些发现为揭示可能在非再生条件下部署的促再生靶点开辟了一条新途径。
