转录因子ATF-3促进神经突生长。

The transcription factor ATF-3 promotes neurite outgrowth.

作者信息

Seijffers Rhona, Allchorne Andrew J, Woolf Clifford J

机构信息

Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.

出版信息

Mol Cell Neurosci. 2006 May-Jun;32(1-2):143-54. doi: 10.1016/j.mcn.2006.03.005. Epub 2006 May 19.

DOI:10.1016/j.mcn.2006.03.005

PMID:16713293

Abstract

Dorsal root ganglion (DRG) neurons regenerate after a peripheral nerve injury but not after injury to their axons in the spinal cord. A key question is which transcription factors drive the changes in gene expression that increase the intrinsic growth state of peripherally injured sensory neurons? A prime candidate is activating transcription factor-3 (ATF-3), a transcription factor that we find is induced in all DRG neurons after peripheral, but not central axonal injury. Moreover, we show in adult DRG neurons that a preconditioning peripheral, but not central axonal injury, increases their growth, correlating closely with the pattern of ATF-3 induction. Using viral vectors, we delivered ATF-3 to cultured adult DRG neurons and find that ATF-3 enhances neurite outgrowth. Furthermore, ATF-3 promotes long sparsely branched neurites. ATF-3 overexpression did not increase c-Jun expression. ATF-3 may contribute, therefore, to neurite outgrowth by orchestrating the gene expression responses in injured neurons.

摘要

背根神经节（DRG）神经元在周围神经损伤后能够再生，但在脊髓中的轴突损伤后则不能再生。一个关键问题是，哪些转录因子驱动基因表达的变化，从而增加周围神经损伤的感觉神经元的内在生长状态？一个主要候选因子是激活转录因子-3（ATF-3），我们发现这是一种转录因子，在周围而非中枢轴突损伤后，所有DRG神经元中都会被诱导产生。此外，我们在成年DRG神经元中发现，预先进行周围而非中枢轴突损伤，会增加它们的生长，这与ATF-3诱导模式密切相关。使用病毒载体，我们将ATF-3导入培养的成年DRG神经元中，发现ATF-3可增强神经突生长。此外，ATF-3促进长出长而稀疏分支的神经突。ATF-3的过表达并未增加c-Jun的表达。因此，ATF-3可能通过协调受损神经元中的基因表达反应，来促进神经突生长。