Investigation of stress-induced microglial activation

在本研究中，我们探讨了小胶质细胞的激活机制。采用RT-PCR、WesternBlotting等方法，对MG 6细胞和原代小胶质细胞进行了体外培养。在细胞系和原代小胶质细胞中，检测到肾上腺素能受体（AR）β 1和β 2的表达，但未检测到β 3。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，我们还研究了肾上腺皮质激素对小胶质细胞活化的影响。结果表明，地塞米松可明显抑制促炎细胞因子白细胞介素-1、白细胞介素-6的表达。此外，我们研究了AR在体内小胶质细胞活化中的参与。在特异性缺乏AR β 1和β 2的双基因敲除小鼠中，小胶质细胞活化不受束缚应激的诱导。结果与野生型小鼠相反，野生型小鼠在脑中表现出显著的应激诱导的小胶质细胞活化。提示在急性应激状态下，小胶质细胞的活化可能通过交感神经系统、AR β 1和β 2进行调节，肾上腺皮质激素可能对小胶质细胞的活化起抑制作用。

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.