Involvement of Activated Microglia in Increased Vulnerability of Motoneurons After Facial Nerve Avulsion in Presymptomatic ALS Model Rats
Involvement of Activated Microglia in Increased Vulnerability of Motoneurons After Facial Nerve Avulsion in Presymptomatic ALS Model Rats
复制标题
症状前 ALS 模型大鼠面神经撕脱后激活的小胶质细胞参与增加运动神经元的脆弱性
作者：
Sanagi T;Nakamura Y;Suzuki E;Uchino S;Aoki M;Warita H;Itoyama Y;Kohsaka S;Ohsawa K.
在各种神经退行性疾病中观察到活化的小胶质细胞，并且认为其参与神经元细胞死亡的过程。与野生型大鼠相比，在表达人突变型Cu 2 +/Zn 2+超氧化物歧化酶1（SOD 1）的症状前转基因大鼠中，面神经撕脱后面神经核运动神经元损伤加速。为了揭示小胶质细胞在运动神经元死亡中的功能作用，我们研究了症状前突变型SOD 1H 46 R（mSOD 1H 46 R）大鼠面神经撕脱后小胶质细胞的反应。撕脱后3天，在野生型和mSOD 1H 46 R大鼠的面核中观察到小胶质细胞簇。与野生型大鼠相比，mSOD 1H 46 R大鼠中小胶质细胞簇、增殖小胶质细胞和运动神经元附着的小胶质细胞数量显著更高。撕脱伤后2周，与野生型大鼠相比，mSOD 1H 46 R大鼠中吞噬细胞标记物ED 1的免疫阳性信号显著更强。此外，与野生型大鼠相比，从mSOD 1H 46 R大鼠制备的原代小胶质细胞显示出增强的吞噬活性。与野生型大鼠相比，mSOD 1H 46 R大鼠面神经核中P2 Y12 mRNA的表达更高。激光显微切割系统显示，与野生型大鼠相比，在撕脱后2天，mSOD 1H 46 R大鼠运动神经元中的ATF 3 mRNA表达更高。这些结果表明，小胶质细胞的激活，以响应早期神经元损伤增加mSOD 1H 46 R大鼠，并建议，增强激活的小胶质细胞可能会导致在mSOD 1H 46 R大鼠撕脱伤后运动神经元的脆弱性增加。© 2012 Wiley Periodicals，Inc.
Activated microglia are observed in various neurodegenerative diseases and are thought to be involved in the processes of neuronal cell death. Motoneuron damage in the facial nuclei after facial nerve avulsion is accelerated in presymptomatic transgenic rats expressing human mutant Cu2+/Zn2+superoxide dismutase 1 (SOD1), compared with that in wild‐type rats. To reveal the functional role of microglia in motoneuronal death, we investigated the microglial response after facial nerve avulsion in presymptomatic mutant SOD1H46R(mSOD1H46R) rats. At 3 days after avulsion, microglial clusters were observed in the facial nuclei of both wild‐type and mSOD1H46Rrats. The numbers of microglial clusters, proliferating microglia, and microglial attachments to motoneurons were significantly higher in mSOD1H46Rrats, compared with those in wild‐type rats. Immunopositive signals for the phagocytic marker ED1 were significantly stronger in mSOD1H46Rrats, compared with that in wild‐type rats, at 2 weeks after avulsion. Furthermore, primary microglia prepared from mSOD1H46Rrats showed enhanced phagocytic activity, compared with that in wild‐type rats. The expression of P2Y12mRNA was higher in the facial nuclei of mSOD1H46Rrats, compared with that in wild‐type rats. A laser microdissection system revealed that the expression of ATF3 mRNA was higher in the motoneurons of mSOD1H46Rrats, compared with that in wild‐type rats, at 2 days after avulsion. These results indicate that microglial activation in response to early neuronal damage increased in mSOD1H46Rrats and suggest that the enhanced activation of microglia may lead to an increase in the vulnerability of motoneurons after avulsion in mSOD1H46Rrats. © 2012 Wiley Periodicals, Inc.