Secreted frizzled-related protein 3 regulates activity-dependent adult hippocampal neurogenesis.
Secreted frizzled-related protein 3 regulates activity-dependent adult hippocampal neurogenesis.
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DOI：
10.1016/j.stem.2012.11.021
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发表时间：
2013-02-07
期刊：
影响因子：
23.9
通讯作者：
Song H
中科院分区：
文献类型：
--
作者：
Jang MH;Bonaguidi MA;Kitabatake Y;Sun J;Song J;Kang E;Jun H;Zhong C;Su Y;Guo JU;Wang MX;Sailor KA;Kim JY;Gao Y;Christian KM;Ming GL;Song H
成体神经发生是从成体神经干细胞产生成熟神经元的过程，与正在进行的神经元回路活动同时进行，并受到各种生理和病理刺激的调节。成年神经发生的连续步骤的活动依赖性调节的生态位机制在很大程度上仍然未知。在这里，我们报告说，神经元的活动减少了分泌型卷曲相关蛋白3（sFRP3），一种天然分泌的Wnt抑制剂的表达高度表达的成年齿状回颗粒神经元。Sfrp3缺失激活静止的放射状神经干细胞并促进成年小鼠海马新生神经元成熟、树突生长和棘形成。此外，sfrp3的减少对于活动诱导的成年神经祖细胞增殖和新神经元发育的加速是必不可少的。我们的研究确定sFRP3作为抑制性小生境因子从当地成熟的齿状颗粒神经元，调节多个阶段的成年海马神经发生，并提出了一种新的活性依赖性机制，通过急性释放紧张性抑制成人神经发生。
Adult neurogenesis, a process of generating mature neurons from adult neural stem cells, proceeds concurrently with ongoing neuronal circuit activity and is modulated by various physiological and pathological stimuli. The niche mechanism underlying activity-dependent regulation of sequential steps of adult neurogenesis remains largely unknown. Here we report that neuronal activity decreases the expression of secreted frizzled-related protein 3 (sFRP3), a naturally secreted Wnt inhibitor highly expressed by adult dentate gyrus granule neurons. Sfrp3 deletion activates quiescent radial neural stem cells and promotes newborn neuron maturation, dendritic growth and spine formation in the adult mouse hippocampus. Furthermore, sfrp3 reduction is essential for activity-induced adult neural progenitor proliferation and acceleration of new neuron development. Our study identifies sFRP3 as an inhibitory niche factor from local mature dentate granule neurons that regulates multiple phases of adult hippocampal neurogenesis and suggests a novel activity-dependent mechanism governing adult neurogenesis via acute release of tonic inhibition.