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首页> 外文期刊>Progress in brain research >Inosine stimulates axon growth in vitro and in the adult CNS.
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Inosine stimulates axon growth in vitro and in the adult CNS.

机译：肌苷在体外和成人中枢神经系统中刺激轴突生长。

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Unlike mammals, lower vertebrates can regenerate their optic nerves and certain other CNS pathways throughout life. To identify the molecular bases of this phenomenon, we developed a cell culture model and found that goldfish retinal ganglion cells will regenerate their axons in response to the purine nucleoside inosine. Inosine acts through a direct intracellular mechanism and induces many of the changes in gene expression that underlie regenerative growth in vivo, e.g., upregulation of GAP-43, T alpha-1 tubulin, and the cell-adhesion molecule, L1. N-kinase, a 47-49-kDa serine-threonine kinase, may mediate the effects of inosine and serve as part of the modular signal transduction pathway that controls axon growth. In vivo, inosine stimulates extensive axon growth in the mature rat corticospinal tract. Following unilateral transection of the corticospinal tract, inosine applied to the intact sensorimotor cortex stimulated layer 5 pyramidal cells to upregulate GAP-43 expression and to sprout axon collaterals. These collaterals crossed the midline at the level of the cervical enlargement and reinnervated regions whose normal connections had been served. Further understanding of the molecular changes that lie upstream and downstream of N-kinase may lead to new insights into the control of axon growth and to novel methods to improve functional outcome in patients with CNS injury.
机译：与哺乳动物不同，低等脊椎动物可以在整个生命中再生其视神经和某些其他CNS途径。为了确定这种现象的分子基础，我们开发了一种细胞培养模型，发现金鱼的视网膜神经节细胞将响应嘌呤核苷肌苷而再生其轴突。肌苷通过直接的细胞内机制起作用并诱导体内再生生长基础的许多基因表达变化，例如GAP-43，T alpha-1微管蛋白和细胞粘附分子L1的上调。 N-激酶是一种47-49-kDa的丝氨酸-苏氨酸激酶，可介导肌苷的作用，并作为控制轴突生长的模块信号转导途径的一部分。在体内，肌苷刺激成熟大鼠皮质脊髓束中广泛的轴突生长。在单侧横断皮质脊髓束后，将肌苷加至完整的感觉运动皮层刺激第5层锥体细胞，以上调GAP-43表达并萌发轴突侧支。这些侧支穿过中线，位于颈椎增大的区域，并且已恢复了正常连接的神经支配区域。对位于N激酶上游和下游的分子变化的进一步了解可能会导致对控制轴突生长的新见解，并为改善CNS损伤患者的功能预后提供新的方法。

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