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.

我们在大鼠海马培养物中首次发现了钙渗透的AMPA受体（Lino等，J。Physiol。，424：151-165，1990）。现在众所周知，受体不仅在神经元中而且在神经胶质细胞中分布广泛。特别是，小脑中的Bergmann Glia大量表达了这些受体。为了将可渗透AMPA受体变成不可渗透的AMPA受体，在这项研究中构建了在Bergmann Glia中表达Glur2的转基因小鼠。首先，我们制作了一个在人神经胶质原纤维酸蛋白（GFAP）启动子的控制下表达大鼠的质粒载体。然后将表达单元注入小鼠的受精卵中。 Glur2表达单元转移到七个后代。将这些转基因小鼠用C57BL6小鼠回合了八代。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，在小脑皮层中强烈表达Glur2，形成片状楔形物，在野生型小鼠中从未观察到。小脑功能的检查正在工作。

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)

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。

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, Wataru Kakegawa, Keisuke Tsuzuki, Meiko Kawamura, Hiroyuki Nawa, Masae lino, Seiji Ozawa: "Sindbis viral-mediated expression of Ca^<2+>-permeable AMPA receptors at hippocampal CA1 synapses and induction of NMDA receptor-inde

Takashi Okada、Nobuaki Yamada、Wataru Kakekawa、Keisuke Tsuzuki、Meiko Kawamura、Hiroyuki Nawa、Masae lino、Seiji Ozawa：“Sindbis 病毒介导的海马 CA1 突触 Ca^<2>-渗透性 AMPA 受体的表达和 NMDA 受体的诱导 -