Nakamichi Noritaka
Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology, Kanazawa, Ishikawa, Japan.
Yakugaku Zasshi. 2011;131(9):1311-6. doi: 10.1248/yakushi.131.1311.
In this review, we have summarized our recent studies on the functionality of ionotropic (iGluR) and metabotropic (mGluR) glutamate receptors expressed by undifferentiated neural progenitor cells (NPC) isolated from embryonic rat and mouse brains. NPC are primitive cells with the self-renewal capacity as well as the multipotentiality to generate different neural lineages including neurons, astrocytes, and oligodendrocytes. Isolated cells were cultured in the presence of growth factors for the formation of round spheres by clustered cells so-called 'neurospheres' under floating conditions. Reverse transcription polymerase chain reaction analyses revealed expression of mRNA for particular iGluR and mGluR subtypes in NPC. Moreover, sustained exposure to an agonist for the N-methyl-D-aspartate receptor (NMDAR) not only inhibited the formation of neurospheres but also promoted differentiation of NPC into cells immunoreactive to a neuronal marker protein on immunocytochemistry and western blot analyses. On the other hand, sustained exposure to an agonist for the group III mGluR subtype led to suppression of proliferation activity in these neurospheres along with facilitation of the subsequent differentiation into astrocytes. Accordingly, glutamate could play a pivotal role in the mechanisms underlying proliferation for self-replication, together with determination of the subsequent differentiation fate toward particular progeny lineages through activation of NMDAR and group III mGluR subtypes in NPC.
在本综述中,我们总结了近期关于从胚胎大鼠和小鼠大脑中分离出的未分化神经祖细胞(NPC)所表达的离子型(iGluR)和代谢型(mGluR)谷氨酸受体功能的研究。NPC是具有自我更新能力以及产生包括神经元、星形胶质细胞和少突胶质细胞在内的不同神经谱系的多能性原始细胞。将分离的细胞在生长因子存在的情况下培养,使其在悬浮条件下通过聚集形成所谓的“神经球”的圆形球体。逆转录聚合酶链反应分析揭示了NPC中特定iGluR和mGluR亚型的mRNA表达。此外,持续暴露于N-甲基-D-天冬氨酸受体(NMDAR)激动剂不仅抑制了神经球的形成,而且在免疫细胞化学和蛋白质印迹分析中促进了NPC向对神经元标记蛋白具有免疫反应性的细胞分化。另一方面,持续暴露于III组mGluR亚型激动剂导致这些神经球的增殖活性受到抑制,同时促进其随后向星形胶质细胞的分化。因此,谷氨酸可能在NPC通过激活NMDAR和III组mGluR亚型进行自我复制的增殖机制以及决定随后向特定子代谱系的分化命运中发挥关键作用。