Nakamichi Noritaka, Takarada Takeshi, Yoneda Yukio
Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology, Ishikawa, Japan.
J Pharmacol Sci. 2009 Jun;110(2):133-49. doi: 10.1254/jphs.08r03cr. Epub 2009 May 30.
In this review, we will summarize our ongoing studies on the functionality of both gamma-aminobutyric acid (GABA) and glutamate receptors expressed by undifferentiated neural progenitor cells isolated from embryonic rodent brains. Cells were cultured with growth factors for the formation of round spheres by clustered cells under floating conditions, whereas a reverse transcription polymerase chain reaction analysis revealed expression of mRNA for particular subtypes of different ionotropic and metabotropic GABA and glutamate receptors in undifferentiated progenitors and neurospheres. Moreover, sustained exposure to either GABAergic or glutamatergic agonists not only modulated the size of neurospheres formed, but also affected spontaneous and induced differentiation of neural progenitor cells into particular progeny cell lineages such as neurons and astroglia. Both GABA and glutamate could play a pivotal role in the mechanisms underlying proliferation for self-replication along with the determination of subsequent differentiation fate toward particular progeny lineages through activation of their receptor subtypes functionally expressed by undifferentiated neural progenitor cells. Accordingly, neurogenesis seems to be also under control by GABAergic and glutamatergic signaling in developing brains as seen with neurotransmission in adult brains.
在本综述中,我们将总结我们正在进行的关于从胚胎啮齿动物大脑中分离出的未分化神经祖细胞所表达的γ-氨基丁酸(GABA)和谷氨酸受体功能的研究。细胞在漂浮条件下与生长因子一起培养,通过聚集细胞形成圆形球体,而逆转录聚合酶链反应分析显示未分化祖细胞和神经球中不同离子型和代谢型GABA和谷氨酸受体特定亚型的mRNA表达。此外,持续暴露于GABA能或谷氨酸能激动剂不仅会调节形成的神经球大小,还会影响神经祖细胞向特定子代细胞谱系(如神经元和星形胶质细胞)的自发和诱导分化。GABA和谷氨酸都可能在自我复制增殖机制中发挥关键作用,并通过激活未分化神经祖细胞功能性表达的受体亚型来决定随后向特定子代谱系的分化命运。因此,正如在成人大脑中的神经传递所见,神经发生似乎也受到发育中大脑中GABA能和谷氨酸能信号的控制。