血清反应因子调节周围轴突损伤时神经元的存活。

Serum response factor modulates neuron survival during peripheral axon injury.

机构信息

Department Molecular Biology, Interfaculty Institute for Cell Biology, Eberhard Karls University Tübingen, Germany.

出版信息

J Neuroinflammation. 2012 Apr 26;9:78. doi: 10.1186/1742-2094-9-78.

BACKGROUND

The transcription factor SRF (serum response factor) mediates neuronal survival in vitro. However, data available so far suggest that SRF is largely dispensable for neuron survival during physiological brain function.

FINDINGS

Here, we demonstrate that upon neuronal injury, that is facial nerve transection, constitutively-active SRF-VP16 enhances motorneuron survival. SRF-VP16 suppressed active caspase 3 abundance in vitro and enhanced neuron survival upon camptothecin induced apoptosis. Following nerve fiber injury in vitro, SRF-VP16 improved survival of neurons and re-growth of severed neurites. Further, SRF-VP16 enhanced immune responses (that is microglia and T cell activation) associated with neuronal injury in vivo. Genome-wide transcriptomics identified target genes associated with axonal injury and modulated by SRF-VP16.

CONCLUSION

In sum, this is a first report describing a neuronal injury-related survival function for SRF.

背景

转录因子 SRF（血清反应因子）介导体外神经元存活。然而，目前可用的数据表明，SRF 在生理脑功能期间对神经元存活的作用不大。

发现

在这里，我们证明在神经元损伤后，即面神经横断，组成型激活的 SRF-VP16 增强运动神经元存活。SRF-VP16 抑制体外活性半胱天冬酶 3 的丰度，并在喜树碱诱导的细胞凋亡时增强神经元存活。在体外神经纤维损伤后，SRF-VP16 改善了神经元的存活和切断的轴突的再生长。此外，SRF-VP16 增强了与体内神经元损伤相关的免疫反应（即小胶质细胞和 T 细胞激活）。全基因组转录组学鉴定了与轴突损伤相关的靶基因，并受 SRF-VP16 调节。