Axotomy induces axonogenesis in hippocampal neurons through STAT3.

After axotomy of embryonic hippocampal neurons in vitro, some of the axotomized axons lose their identity, and new axons arise and grow. This axotomy-induced axonogenesis requires importin, suggesting that some injury-induced signals are transported via axons to elicit axonogenesis after axotomy. In this study, we show that STAT3 is activated in response to axotomy. Because STAT3 was co-immunoprecipitated with importin β in the axotomized neurons, we suggest that STAT3 is retrogradely transported as molecular cargo of importin α/β heterodimers. Indeed, inhibition of importin α binding with STAT3 resulted in the attenuation of axonogenesis. Silencing STAT3 blocked the axonogenesis, demonstrating that STAT3 is necessary for axotomy-induced axonogenesis. Furthermore, the overexpression of STAT3 enhanced axotomy-induced axonogenesis. Taken together, these results demonstrate that activation and retrograde transport of STAT3 in injured axons have key roles in the axotomy-induced axonogenesis of hippocampal neurons.

在体外的胚胎海马神经元的轴旋转后，某些轴突轴突会失去其身份，而新的轴突出现并生长。在β中轴向神经元，我们认为STAT3是进口蛋白α/β的分子货物的逆转，确实抑制了进口的α与STAT3的结合。 Esis结果表明，在受伤的轴突中Stat3的激活和逆行转运在轴切开术引起的海马神经元的轴突生成中具有关键作用。