Park Ji-Young, Kim Hee Young, Jou Ilo, Park Sang Myun
Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 442-721, Republic of Korea.
Brain Res. 2008 Dec 9;1244:13-23. doi: 10.1016/j.brainres.2008.09.072. Epub 2008 Oct 7.
Microglia are immunologically competent cells in the central nervous system and considered to be a key player in brain inflammation. The morphological change of microglia has been shown to be linked to functional phenotypes both in vivo and in vitro. As an attempt to identify factors that regulate microglial morphology, we investigated the effect of gangliosides on microglial ramification in vitro. Brain gangliosides mixture and GM1 induced typical ramification of cultured rat primary microglia, however, GD1a and GT1b did not. Although GM1 significantly induced the expression of neurotrophin-3 (NT-3), NT-3 did not induce typical morphological changes in cultured rat primary microglia. SB203580 (an inhibitor of p38), and paclitaxel and nocodazole (microtubule-disrupting drugs) inhibited GM1-induced microglial ramification, but Jaki (an inhibitor of JAK), PD98059 (an inhibitor of Erk1/2), SP600125 (an inhibitor of JNK), and cytochalasin B and latrunculin B (actin polymerization inhibitors) did not, suggesting that GM1 induced ramification of microglia in p38- and microtubule-dependent manner. This in vitro system would be helpful in understanding the mechanisms of microglial ramification and physiological roles of gangliosides in microglia.
小胶质细胞是中枢神经系统中具有免疫活性的细胞，被认为是脑部炎症的关键参与者。小胶质细胞的形态变化已被证明在体内和体外均与功能表型相关。作为识别调节小胶质细胞形态因素的尝试，我们研究了神经节苷脂对体外培养的小胶质细胞分支的影响。脑源性神经节苷脂混合物和GM1可诱导培养的大鼠原代小胶质细胞出现典型的分支，然而，GD1a和GT1b则不能。尽管GM1显著诱导了神经营养因子-3（NT-3）的表达，但NT-3并未在培养的大鼠原代小胶质细胞中诱导典型的形态变化。SB203580（一种p38抑制剂）、紫杉醇和诺考达唑（微管破坏药物）可抑制GM1诱导的小胶质细胞分支，但Jaki（一种JAK抑制剂）、PD98059（一种Erk1/2抑制剂）、SP600125（一种JNK抑制剂）以及细胞松弛素B和Latrunculin B（肌动蛋白聚合抑制剂）则不能，这表明GM1以p38和微管依赖性方式诱导小胶质细胞分支。这种体外系统将有助于理解小胶质细胞分支的机制以及神经节苷脂在小胶质细胞中的生理作用。
