Dynamic Changes of Astrocytes and Adenosine Signaling in Rat Hippocampus in Post-status Epilepticus Model of Epileptogenesis
Dynamic Changes of Astrocytes and Adenosine Signaling in Rat Hippocampus in Post-status Epilepticus Model of Epileptogenesis
复制标题
DOI：
10.1007/s10571-018-0590-9
复制
发表时间：
2018-08-01
影响因子：
4
通讯作者：
Jiang, Li
中科院分区：
文献类型：
--
作者：
Hong, Siqi;Li, Tingsong;Jiang, Li
探索癫痫的发生发展具有重要意义，而腺苷和腺苷激酶（ADK）系统似乎在这一过程中发挥着关键作用。本研究的目的是探讨癫痫发生后（SE）模型中大鼠海马癫痫发生过程中星形胶质细胞和腺苷信号传导的动态变化。在SE诱导后第1天(致痫急性期)、5天(潜伏期)、4周(慢性期)和8周(致痫后期慢性期)建立大鼠SE模型并处死进行实验。采用免疫荧光染色、高效液相色谱和蛋白质印迹法评估海马星形胶质细胞、腺苷、ADK和ADK受体（包括A1R、A2aR、A2bR和A3R）的变化。胶质纤维酸性蛋白的表达水平从潜伏期到慢性晚期显着增加。急性期腺苷浓度急剧升高，SE后其余各期逐渐下降，慢性期末期显着低于对照组。 SE后模型中A1R和A2aR的蛋白水平在急性期增加，而A2bR和A3R蛋白表达在SE后癫痫发生后的潜伏期、慢性期和慢性晚期降低。 ADK 蛋白表达在 SE 癫痫发生后的潜伏期、慢性期和慢性晚期显着增加。总之，SE后急性期腺苷水平和A1R和A2R蛋白表达显着增加。在 SE 癫痫发生的剩余阶段，星形胶质细胞、腺苷、腺苷受体和 ADK 之间存在不平衡。 ADK/腺苷系统的调节可能为癫痫发生提供潜在的治疗策略。
It is of great importance to explore the development of epileptogenesis, and the adenosine and adenosine kinase (ADK) system seems to play a key role in this process. The aim of this study is to explore the dynamic changes of astrocytes and adenosine signaling during epileptogenesis in rat hippocampus in a post-status epileptogenesis (SE) model. Rat SE models were built and killed for experiments at 1 day (acute phase of epileptogenesis), 5 days (latent phase), 4 weeks (chronic phase), and 8 weeks (late chronic phase of epileptogenesis) after SE induction. Immunofluorescence staining, high-performance liquid chromatography, and Western blotting were performed to assess changes of astrocytes, adenosine, ADK, and ADK receptors (including A1R, A2aR, A2bR, and A3R) in hippocampus. The expression level of glial fibrillary acidic protein significantly increased from latent to late chronic phase. The concentration of adenosine sharply increased in acute phase and gradually decreased in the remaining phases of post-SE, being significantly lower than in the control group in late chronic phase. Protein levels of A1R and A2aR in post-SE models increased in acute phase, whereas A2bR and A3R protein expression decreased in latent phase, chronic phase, and late chronic phase following post-SE epileptogenesis. Protein expression of ADK significantly increased during latent phase, chronic phase, and late chronic phase of post-SE epileptogenesis. In conclusion, the levels of adenosine and protein expression of A1R and A2R significantly increased during acute phase of post-SE. During the remaining phases of post-SE epileptogenesis, there was imbalance among astrocytes, adenosine, adenosine receptors, and ADK. Regulation of the ADK/adenosine system may provide potential treatment strategies for epileptogenesis.