Role of calcium-permeable AMPA receptors in glial cells

钙渗透性 AMPA 受体在神经胶质细胞中的作用

• 批准号: 13680862
• 负责人: TSUZUKI Keisuke
• 金额: $ 2.05万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680862/
• 关键词: Bergmann glia; calcium; glial fibrillary acidic protein; transgenic mice; glutamate receptor; グリア線維酸性タンパク質

We found calcium-permeable AMPA receptors for the first time in rat hippocampal culture (lino et al., J. Physiol., 424 : 151-165, 1990). Now it is known that receptor is widely distributed not only in neurons but also in glial cells. In particular, Bergmann glia in the cerebellum abundantly expresses these receptors. In order to change the calcium permeable AMPA receptors into impermeable ones, transgenic mice that expressed GluR2 in Bergmann glia were constructed in this study. First, we made a plasmid vector that express GluR2_<flip> of the rat under the control of the human glial fibrillary acid protein (GFAP) promoter. Then the expression unit was injected into fertilized eggs of the mouse. GluR2 expression unit was transferred into seven offspring. These transgenic mice were backcrossed with C57BL6 mice for eight generations. The transgenic mice have smaller brains compared with wild type mice. Matching with the region of GFAP, GluR2 were strongly expressed in cerebellar cortex, forming patchy wedges, which were never observed in wild type mice. Examination of cerebellar function is under work.

我们首次在大鼠海马培养物中发现了钙渗透性 AMPA 受体（lino 等人，J.Physiol.，424：151-165，1990）。目前已知受体不仅广泛分布于神经元中，而且广泛分布于神经胶质细胞中。特别是，小脑中的伯格曼神经胶质细胞大量表达这些受体。为了将钙可渗透的AMPA受体改变为不可渗透的，本研究构建了伯格曼胶质细胞中表达GluR2的转基因小鼠。首先，我们制作了在人胶质纤维酸性蛋白（GFAP）启动子控制下表达大鼠GluR2_<flip>的质粒载体。然后将表达单元注射到小鼠的受精卵中。 GluR2 表达单位被转移到七个后代中。这些转基因小鼠与 C57BL6 小鼠回交八代。与野生型小鼠相比，转基因小鼠的大脑较小。与 GFAP 区域相匹配，GluR2 在小脑皮质中强烈表达，形成斑片状楔形，这在野生型小鼠中从未观察到。小脑功能检查正在进行中。

项目成果

Yutaka Saito, Keisuke Tsuzuki, Nobuaki Yamada, Haruo Okado, Akiko Miwa, Fumio Goto, Seiji Ozawa: "Transfer of NMDAR2 cDNAs increases endogenous NMDAR1 protein and induces expression of functional NMDA receptors in PC12 cells"Brain Res. Mol. Brain Res.. 11

Yutaka Saito、Keisuke Tsuzuki、Nobuaki Yamada、Haruo Okado、Akiko Miwa、Fumio Goto、Seiji Ozawa：“NMDAR2 cDNA 的转移会增加内源性 NMDAR1 蛋白并诱导 PC12 细胞中功能性 NMDA 受体的表达”Brain Res。

Anzai, T. et al.: "Overexpression of Ca^<2+>-permeable AMPA receptor promotes delayed cell death of hippocampal CA1 neurons following transient forebrain ischemia."Neurosci Res.. 46. 41-51 (2003)

Anzai，T.等人：“Ca^2-渗透性AMPA受体的过度表达促进短暂前脑缺血后海马CA1神经元的延迟细胞死亡。”Neurosci Res.. 46. 41-51 (2003)

Wataru Kakegawa, Keisuke Tsuzuki, Masae lino, Seiji Ozawa: "Functional NMDA receptor channels generated by NMDAR2B gene transfer in rat cerebellar Purkinje cells"Eur. J. Neurosci.. 17(4). 887-891 (2003)

Wataru Kakekawa、Keisuke Tsuzuki、Masae lino、Seiji Ozawa：“大鼠小脑浦肯野细胞中 NMDAR2B 基因转移产生的功能性 NMDA 受体通道”Eur。

Takashi Okada, Nobuaki Yamada, Keisuke Tsuzuki, Hiroshi M. Horikawa, Kohichi Tanaka, Seiji Ozawa: "Long-term potentiation in the hippocampal CA1 area and dentate gyrus plays different roles in spatial learning"Eur. J. Neurosci.. 17(2). 341-349 (2003)

Takashi Okada、Nobuaki Yamada、Keisuke Tsuzuki、Hiroshi M. Horikawa、Kohichi Tanaka、Seiji Ozawa：“海马 CA1 区和齿状回的长时程增强在空间学习中发挥不同的作用”Eur。

Ishiuchi, S. et al.: "Blockage of Ca^<2+>-permeable AMPA receptors suppresses migration and induces apoptosis in human glioblastoma cells."Nat.Med.. 8. 971-978 (2002)

Ishiuchi，S.等人：“阻断Ca 2+ -渗透性AMPA受体可抑制人胶质母细胞瘤细胞的迁移并诱导细胞凋亡。”Nat.Med.. 8. 971-978 (2002)