Investigation of stress-induced microglial activation

应激诱导的小胶质细胞激活的研究

基本信息

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

项目摘要

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，我们研究了小胶质激活机制。使用小胶质细胞系（MG6）以及原代小胶质细胞，我们使用了RT-PCR，Western blotting。在细胞系和原发性小胶质细胞中，检测到肾上腺素能受体（AR）β1和β2的表达，但未检测到beta3。然后，我们为AR，异丙肾上腺素施用了激动剂。结果表明，异丙肾上腺素不影响白介素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，肾上腺类固醇，右卫唑酮的促炎细胞因子（例如白介素-1，白介素-6）的表达显着抑制。此外，我们研究了AR在体内的小胶质细胞激活中的参与。在特别缺乏AR Beta1和beta2的双基因敲除小鼠中，小胶质细胞激活不是由约束应力暴露引起的。结果与野生型小鼠相反，野生型小鼠表现出明显的应激诱导的小胶质细胞活化。因此，有人提出，在急性应力下，小胶质细胞激活可以通过交感神经系统，ARβ1和β2进行调节。还建议肾上腺糖皮质激素可能在小胶质细胞激活中起抑制性作用。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Ibuprofen ameliorates protein aggregation and astrocytic gliosis, but not cognitive dysfunction, in a transgenic mouse expressing dementia with Lewy bodies-linked P123H b-synuclein

在表达路易体相关 P123H b-突触核蛋白痴呆的转基因小鼠中，布洛芬可改善蛋白质聚集和星形胶质细胞增生，但不能改善认知功能障碍

DOI：
10.1016/j.neulet.2012.03.037
发表时间：
2012
期刊：
Neurosci Lett
影响因子：
2.5
作者：
S ekiyama K;Fujita M;Sekigawa A;Takamatsu Y;Waragai M;Takenouchi T;Sugama S;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

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

P2X7 Receptor Signaling Pathway as a Therapeutic Target for Neurodegenerative Diseases

DOI：
10.1007/s00005-010-0069-y
发表时间：
2010-02
期刊：
Archivum Immunologiae et Therapiae Experimentalis
影响因子：
3.2
作者：
T. Takenouchi;K. Sekiyama;A. Sekigawa;M. Fujita;M. Waragai;S. Sugama;Y. Iwamaru;H. Kitani;M. Hashim
通讯作者：
T. Takenouchi;K. Sekiyama;A. Sekigawa;M. Fujita;M. Waragai;S. Sugama;Y. Iwamaru;H. Kitani;M. Hashim

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