Study on the glutamate-induced spinal neurodysfunction.

谷氨酸所致脊髓神经功能障碍的研究。

• 批准号: 23590113
• 负责人: SUZUKI Takeshi
• 金额: $ 3.41万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590113/
• 关键词: 薬理学; グルタミン酸; 情報伝達; 神経変性疾患; 興奮毒性; 神経炎症; ATP; ミクログリア; パロキセチン; 脊髄

In this study, we investigated mechanisms underlying the dysfunction of glutamate transmission under the inflammatory condition in the spinal cord. We also examined effects of drugs acting on CNS functions. We made in vitro inflammation model using co-culture comprised of astrocytes, microglia and neurons obtained from newborn rat brains. Inflammation decreased glutamate transport by down-regulation of GLAST induced by high-concentration of extracellular glutamate released from activated microglia in this co-culture. Among centrally acting drugs including antidepressants we tested, only paroxetine inhibited the inflammation-induced glutamate release from activated microglia and prevented the decrease in the glutamate transport. We also demonstrated that ATP is one of the factor that made the neural inflammation worse.

在这项研究中，我们研究了炎症条件下脊髓谷氨酸传递功能障碍的机制。我们还研究了药物对中枢神经系统功能的影响。我们采用星形胶质细胞、小胶质细胞和新生大鼠脑内神经元共培养的方法建立了体外炎症模型。在这种共培养中，炎症通过下调GLAST来减少谷氨酸的转运，GLAST是由激活的小胶质细胞释放的高浓度细胞外谷氨酸引起的。在我们测试的包括抗抑郁药在内的中枢作用药物中，只有帕罗西汀能抑制炎症诱导的小胶质细胞释放谷氨酸，并阻止谷氨酸转运的减少。我们还证明了三磷酸腺苷是加重神经炎症的因素之一。

项目成果

抗うつ薬とP2X4受容体の相互作用の比較検討

抗抑郁药与P2X4受体相互作用的比较研究

• 发表时间: 2014
• 作者: 笠原由佳;三浦麻利衣;最上由香里;関野祐子;佐藤薫;鈴木岳之
• 通讯作者: 鈴木岳之

Effect of antidepressants on the functional impairment of L-glu transporters under the inflammatory condition.

抗抑郁药对炎症条件下 L-glu 转运蛋白功能损伤的影响。

• 发表时间: 2012
• 作者: 藤森康希;高木淳平;佐藤薫;鈴木岳之
• 通讯作者: 鈴木岳之

L-glutamate released from activated microglia downregulates astrocytic L-glutamate transporter expression in neuroinflammation: the 'collusion' hypothesis for increased extracellular L-glutamate concentration in neuroinflammation.

• DOI: 10.1186/1742-2094-9-275
• 发表时间: 2012-12-23
• 期刊: Journal of neuroinflammation
• 影响因子: 9.3
• 作者: Takaki J;Fujimori K;Miura M;Suzuki T;Sekino Y;Sato K
• 通讯作者: Sato K

Cell-autonomous enhancement of glutamate-uptake by female astrocytes.

雌性星形胶质细胞对谷氨酸摄取的细胞自主增强。

• DOI: 10.1007/s10571-012-9829-z
• 发表时间: 2012
• 期刊: Molecular and Cellular Neurobiology
• 作者: Morizawa;Y
• 通讯作者: Y

P2X4 receptor -mediated acceleration of microglial activation is important for the L-glutamate release from activated microglia in the early stage of inflammation

P2X4 受体介导的小胶质细胞活化加速对于炎症早期活化的小胶质细胞释放 L-谷氨酸非常重要

• 发表时间: 2013
• 作者: Sato K;Fujimori K;Takaki J;Suzuki T;Sekino Y
• 通讯作者: Sekino Y