Group III metabotropic glutamate receptor activation suppresses self‐replication of undifferentiated neocortical progenitor cells
Group III metabotropic glutamate receptor activation suppresses self‐replication of undifferentiated neocortical progenitor cells
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DOI：
10.1111/j.1471-4159.2008.05289.x
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发表时间：
2008-06
影响因子：
4.7
通讯作者：
N. Nakamichi;Kohei Yoshida;Yukichi Ishioka;Juliet O. Makanga;Masaki Fukui;M. Yoneyama;T. Kitayama;N. Nakamura;H. Taniura;Y. Yoneda
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文献类型：
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作者：
N. Nakamichi;Kohei Yoshida;Yukichi Ishioka;Juliet O. Makanga;Masaki Fukui;M. Yoneyama;T. Kitayama;N. Nakamura;H. Taniura;Y. Yoneda
我们评估了可能的功能表达代谢型谷氨酸受体（mGluRs）的胚胎小鼠新皮层的神经祖细胞。在与表皮生长因子一起培养的过程中，在未分化细胞和成簇细胞形成的神经球中观察到I、II和III组mGluRs的组成型表达。在这些神经球中，第III组mGluR激动剂1 - 2-氨基-4-膦酰基丁酸酯在1-100 μM下显著降低增殖活性而不诱导细胞死亡，第I组和第II组mGluR激动剂无效。毛喉素和第III组mGluR拮抗剂单独显著增加增殖，但显著阻止1 - 2-氨基-4-膦酰基丁酸酯的抑制。III组mGluR的激活显著降低细胞周期调节因子cyclinD 1的mRNA表达，除了抑制多能P19祖细胞中cAMP介导的cyclinD 1基因的反式激活。III组mGluR的预先激活导致神经元标记物免疫反应性细胞数量显著减少，而星形胶质细胞标记物的免疫反应性细胞数量增加，与分化诱导剂无关。这些结果表明，III组mGluR可能在功能上表达，以通过与cAMP形成相关的机制抑制自我更新能力，并促进随后在神经祖细胞中分化为星形胶质细胞谱系。
We evaluated the possible functional expression of metabotropic glutamate receptors (mGluRs) by neural progenitors from embryonic mouse neocortex. Constitutive expression was seen with group I, II, and III mGluRs in undifferentiated cells and neurospheres formed by clustered cells during culture with epidermal growth factor. The group III mGluR agonist, l‐2‐amino‐4‐phosphonobutyrate, drastically reduced proliferation activity at 1–100 μM without inducing cell death, with group I and group II mGluR agonists being ineffective, in these neurospheres. Both forskolin and a group III mGluR antagonist significantly increased the proliferation alone, but significantly prevented the suppression by l‐2‐amino‐4‐phosphonobutyrate. Activation of group III mGluR significantly decreased mRNA expression of the cell cycle regulator cyclinD1, in addition to inhibiting the transactivation mediated by cAMP of cyclinD1 gene in the pluripotent P19 progenitor cells. Prior activation of group III mGluR led to a significant decrease in the number of cells immunoreactive for a neuronal marker, with an increase in that for an astroglial marker irrespective of differentiation inducers. These results suggest that group III mGluR may be functionally expressed to suppress self‐renewal capacity through a mechanism related to cAMP formation with promotion of subsequent differentiation into astroglial lineage in neural progenitors.