Gianola Sara, Rossi Ferdinando
Department of Neuroscience and Rita Levi Montalcini Center for Brain Repair, University of Turin, Turin, Italy.
Exp Neurol. 2002 Jul;176(1):25-40. doi: 10.1006/exnr.2002.7924.
Long-distance axon regeneration requires the activation of a specific set of neuronal growth-associated genes. Adult Purkinje cells fail to upregulate these molecules in response to axotomy and show extremely weak regenerative properties. Nevertheless, starting from several months after injury, transected Purkinje axons undergo spontaneous sprouting. Here, we asked whether long-term injured Purkinje cells acquire novel intrinsic growth properties that enable them to upregulate growth-associated genes and sustain axon regeneration. To test this hypothesis, we examined axon growth and cell body changes in adult rat Purkinje neurons following axotomy and implantation of embryonic neocortical tissue or Schwann cells into the injury track. Purkinje cells that survived over 6 months after injury/transplantation displayed profuse sprouting in the injured cerebellum and developed extensive networks of terminal branches into embryonic neocortical grafts. In addition, severed Purkinje axons exposed to these transplants 6 months after injury grew faster than their counterparts confronted with the same environment immediately after axotomy. Nevertheless, long-term injured Purkinje cells failed to regenerate stem neurites into Schwann cell grafts, and, under all experimental conditions, they did not upregulate growth-associated molecules, including c-Jun, GAP-43, SNAP-25, and NADPH-diaphorase. These results indicate that the long-term injured Purkinje cells remain unable to activate the gene program required to sustain axon regeneration and their plasticity is restricted to terminal arbor remodeling. We propose that the delayed growth of injured Purkinje cells reflects an adaptive phenomenon by which the severed axon stump develops a new terminal arbor searching for alternative connections with local partners.
长距离轴突再生需要激活一组特定的与神经元生长相关的基因。成年浦肯野细胞在轴突切断后无法上调这些分子，并且表现出极其微弱的再生特性。然而，从损伤后的几个月开始，横断的浦肯野轴突会发生自发芽生。在这里，我们探讨长期受损的浦肯野细胞是否获得了新的内在生长特性，使其能够上调与生长相关的基因并维持轴突再生。为了验证这一假设，我们研究了成年大鼠浦肯野神经元在轴突切断以及将胚胎新皮质组织或雪旺细胞植入损伤部位后的轴突生长和细胞体变化。在损伤/移植后存活超过6个月的浦肯野细胞在受损的小脑中大量芽生，并在胚胎新皮质移植物中形成广泛的终末分支网络。此外，损伤6个月后暴露于这些移植的切断浦肯野轴突比轴突切断后立即处于相同环境的对应轴突生长得更快。然而，长期受损的浦肯野细胞无法将干神经突再生到雪旺细胞移植物中，并且在所有实验条件下，它们都没有上调包括c-Jun、GAP-43、SNAP-25和NADPH-黄递酶在内的与生长相关的分子。这些结果表明，长期受损的浦肯野细胞仍然无法激活维持轴突再生所需的基因程序，并且它们的可塑性仅限于终末树突重塑。我们提出，受损浦肯野细胞的延迟生长反映了一种适应性现象，即切断的轴突残端形成新的终末树突以寻找与局部伙伴的替代连接。
