Investigation of stress-induced microglial activation

应激诱导的小胶质细胞激活的研究

• 批准号: 20500359
• 负责人: SUGAMA Shuei
• 金额: $ 2.91万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20500359/
• 关键词: グリア; 神経免疫学; 拘束ストレス; ミクログリア; ノルアドレナリン受容体; 副腎皮質ステロイド; LPS; イソプロテレノロール; ダブルノックアウトマウス; RT-PCR; ストレス; アストロサイト; 寒冷刺激; インターロイキン1β; 海馬; 視床下部; 交感神経系; アストログリア; 中枢神経; サイトカイン; インターロイキン1; 感染; 中心灰白質; Fos蛋白; グルタミン酸; ノルアドレナリン

In the present study, we investigated microglial activation mechanism. With using microglia cell-line(MG6) as well as primary microglial cells, we employed RT-PCR, Western Blotting. Both in cell line and primary microglia, the expression of adrenergic receptor(AR) beta1 and beta2, but not beta3, was detected. Then, we administered an agonist for AR, isoproterenol. The result showed that isoproterenol did not affect the induction of interleukin-6.In addition, we studied an effect of adrenal steroid on microglial activation. It was shown that the expression of proinflammatory cytokines, such as interleukin-1, interleukin-6, was significantly inhibited by the adrenal steroid, dexamethazone. Furthermore, we studied the involvement of AR in microglial activation in vivo. In double knockout mouse that specifically lacks AR beta1 and beta2, microglial activation was not induced by exposure of restraint stress. The result was in contrast to that of wild type mouse which demonstrated significant stress-induced microglial activation in the brain. Thus, it was suggested that, in acute stress, microglial activation may be modulated through sympathetic nervous system, AR beta 1 and beta2.It was also suggested that adrenal glucocorticoids may play inhibitory roles in microglial activation.

在本研究中，我们研究了小胶质细胞的激活机制。我们使用小胶质细胞系（MG6）和原代小胶质细胞，采用RT-PCR、Western Blotting。在细胞系和原代小胶质细胞中，均检测到肾上腺素受体（AR）β1和β2的表达，但未检测到β3的表达。然后，我们给予 AR 激动剂异丙肾上腺素。结果表明，异丙肾上腺素不影响白细胞介素6的诱导。此外，我们研究了肾上腺类固醇对小胶质细胞活化的影响。结果表明，促炎细胞因子的表达，如白细胞介素1、白细胞介素6，被肾上腺类固醇地塞米松显着抑制。此外，我们研究了 AR 在体内参与小胶质细胞激活的过程。在特异性缺乏 AR beta1 和 beta2 的双基因敲除小鼠中，暴露束缚应激不会诱导小胶质细胞活化。结果与野生型小鼠的结果相反，野生型小鼠表现出大脑中显着的应激诱导的小胶质细胞激活。因此，有人提出，在急性应激时，小胶质细胞的活化可能通过交感神经系统、ARβ1和β2进行调节。也有人提出，肾上腺糖皮质激素可能在小胶质细胞的活化中发挥抑制作用。

项目成果

P2X7 receptor signaling pathway as a therapeutic target for neurodegenerative diseases

P2X7受体信号通路作为神经退行性疾病的治疗靶点

• 发表时间: 2010
• 作者: Takenouchi T; Sekiyama K; Sekigawa A; Fujita M; Waragai M; Sugama S; Iwamaru Y; Kitani H; Hashimot M
• 通讯作者: Hashimot M

Differential microglial activation between acute stress and lipopolysaccharide administration

急性应激和脂多糖给药之间的差异小胶质细胞激活

• DOI: 10.1016/j.jneuroim.2008.11.007
• 发表时间: 2009
• 作者: Sugama S; Takenouchi T; Conti B; Hashimoto M
• 通讯作者: Hashimoto M

Immunological responses of astroglia in the rat brain under acute stress : interletikin-1 beta co-localized in astroglia

急性应激下大鼠脑星形胶质细胞的免疫反应：白细胞介素-1β共定位于星形胶质细胞

• 发表时间: 2011
• 影响因子: 3.3
• 作者: Sugama S; Takenouchi T; Sekiyama K; Kitani H; Hashimoto M
• 通讯作者: Hashimoto M

Mapping of the full length and the truncated interleukin-18 receptor alpha in the mouse brain.

小鼠大脑中白细胞介素 18 受体 α 的全长和截短图谱。

• 发表时间: 2009
• 作者: Alboni S; Cervia D; Ross B; Montanari C; Gonzalex AS; Sanchez
• 通讯作者: Sanchez

The role of P2X7 receptor impairs lysosomal functions and stimulates the release of autophagolysosomes in microglial cells

P2X7受体的作用损害溶酶体功能并刺激小胶质细胞自噬溶酶体的释放

• 发表时间: 2009
• 作者: Takenouchi T; Fujita M; Sugama S; Kitani H; Hashimoto M.
• 通讯作者: Hashimoto M.