Chen X, Liu Y, Zhang Z, Miao X, Tian Y, Yao L, Liu J, Lu H, Liu Y
Xi'an Jiaotong University Health Science Center Institute of Neurobiology Xi'an China.
Shaanxi Provincial People's Hospital Department of Neurosurgery Xi'an China.
Cell Mol Biol (Noisy-le-grand). 2016 Mar 31;62(3):105-14.
Neural stem cells (NSCs) reside in not only developing, but also adult brain with specialized microenvironments that regulate their function. In vitro and in vivo studies have revealed strong regulatory links between hypoxic/ischemic insults and activation of NSCs. However, the underlying mechanisms remain unclear. Here, we show that proliferating NSCs isolated from rat E15.5 cortex expressed functional metabotropic glutamate receptor (mGluR) subtype 3-7. Hypoxic exposure regulated their expression in NSCs in mRNA and protein levels. Activation of mGluRs by glutamate or Trans-ACPD (a non subtype-selective mGluRs agonist) sensitized NSCs to the growth effects of hypoxia. Pharmacological blockade of ionotropic glutamate receptor (iGluR) using MK-801 did not attenuate the action of glutamate in NSCs. Furthemore, we used the group specific mGluR agonists DHPG, LY 379268 and L-AP4 to explore which mGluR subtypes are responsible for stimulating NSCs proliferation after hypoxia. The results suggested that hypoxia increased expression of group I mGluR5 and significantly enhanced the NSCs proliferation. We conclude that hypoxia regulates the expression of mGluRs in proliferating NSCs and the dynamic expression of mGluRs induced by hypoxia may be one of the mechanisms of hypoxia stimulated NSCs activation. Regulation of mGluRs in NSCs might be a useful tool in the experimental cell therapy of hypoxic/ischemic injuries of CNS.
神经干细胞（NSCs）不仅存在于发育中的大脑，也存在于成体大脑中，其具有调节自身功能的特殊微环境。体外和体内研究均揭示了缺氧/缺血性损伤与神经干细胞激活之间存在紧密的调控联系。然而，其潜在机制仍不清楚。在此，我们发现从大鼠胚胎第15.5天皮层分离出的增殖期神经干细胞表达功能性代谢型谷氨酸受体（mGluR）亚型3 - 7。缺氧暴露在mRNA和蛋白质水平上调节了神经干细胞中这些受体的表达。谷氨酸或反式-ACPD（一种非亚型选择性mGluR激动剂）激活mGluRs可使神经干细胞对缺氧的生长效应更敏感。使用MK - 801对离子型谷氨酸受体（iGluR）进行药理学阻断并未减弱谷氨酸对神经干细胞的作用。此外，我们使用了组特异性mGluR激动剂DHPG、LY 379268和L - AP4来探究哪种mGluR亚型负责在缺氧后刺激神经干细胞增殖。结果表明，缺氧增加了I组mGluR5的表达并显著增强了神经干细胞的增殖。我们得出结论，缺氧调节增殖期神经干细胞中mGluRs的表达，缺氧诱导的mGluRs动态表达可能是缺氧刺激神经干细胞激活的机制之一。调节神经干细胞中的mGluRs可能是中枢神经系统缺氧/缺血性损伤实验性细胞治疗中的一种有用工具。
