GDF10 is a signal for axonal sprouting and functional recovery after stroke.
GDF10 is a signal for axonal sprouting and functional recovery after stroke.
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DOI：
10.1038/nn.4146
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发表时间：
2015-12
影响因子：
25
通讯作者：
Carmichael ST
中科院分区：
文献类型：
--
作者：
Li S;Nie EH;Yin Y;Benowitz LI;Tung S;Vinters HV;Bahjat FR;Stenzel-Poore MP;Kawaguchi R;Coppola G;Carmichael ST
中风会产生一个有限的神经修复过程。梗死区附近皮质中的轴突萌发是这一恢复过程的一部分，但启动轴突萌发的信号尚不清楚。生长分化因子10(GDF10)在小鼠、非人灵长类和人类脑梗塞周围神经元中均有表达。GDF10通过转化生长因子βRI/II信号通路促进体外培养的小鼠、大鼠和人神经元的轴突生长。利用药物遗传学功能得失研究，GDF10可产生轴突萌发并增强中风后的功能恢复；击倒GDF10可阻止轴突萌发并降低恢复速度。来自梗塞周围皮质神经元的RNA-SEQ表明，GDF10下调PTEN，上调PI3激酶信号，并诱导特定的轴突引导分子。对GDF10转录组的非监督全基因组关联分析表明，它与神经发育无关，但可能与其他中枢神经系统损伤模式部分重叠。GDF10是卒中诱导的轴突萌发和功能恢复的信号。
Stroke produces a limited process of neural repair. Axonal sprouting in cortex adjacent to the infarct is part of this recovery process, but the signal that initiates axonal sprouting is not known. Growth and Differentiation Factor 10 (GDF10) is induced in peri-infarct neurons in mouse, non-human primate and human. GDF10 promotes axonal outgrowth in vitro in mouse, rat and human neurons through TGFβRI/II signaling. Using pharmacogenetic gain and loss of function studies, GDF10 produces axonal sprouting and enhanced functional recovery after stroke; knocking down GDF10 blocks axonal sprouting and reduces recovery. RNA-seq from peri-infarct cortical neurons indicates that GDF10 downregulates PTEN and upregulates PI3 kinase signaling and induces specific axonal guidance molecules. Unsupervised genome-wide association analysis of the GDF10 transcriptome shows that it is not related to neurodevelopment but may partially overlap with other CNS injury patterns. GDF10 is a stroke-induced signal for axonal sprouting and functional recovery.