Zhan Xian-Feng, Li Bing, Wu Bei, Peng Yu-Ping, Qiu Yi-Hua
Department of Physiology, School of Medical Sciences of Nantong University, Nantong 226001, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2010 Aug;26(3):365-9.
To study the effect and the possible mechanism of IL-6 on NMDA-excited neuronal discharges of rats in vitro.
The cerebellar slices were prepared and spontaneous discharges of single cerebellar interposed nuclear (IN) neurons were recorded by extracellular recordings. The cerebellar slices were perfused with artificial cerebral spinal fluid (ACSF) containing N-methyl-D-aspartate (NMDA), IL-6, JAK inhibitor AG490. The changes in firing activities of the neurons treated with the drugs were recorded. The levels of phosphorylation at serine 897 site of NMDA receptor subunit 1 (NR1) in the neurons treated with various drugs mentioned above were detected by Western blot.
The discharge rates of the neurons that were treated with IL-6 together with NMDA were significantly lower than those of the neurons treated with NMDA alone. AG490 partially blocked the inhibitory effect of IL-6 on the NMDA-stimulated neuronal firing activity. The treatment of the neurons with IL6 and NMDA led to a concentration-dependent suppression of the phospho-NR1 expression relative to those neurons treated with NMDA alone. AG490 blocked the effect of the IL-6-induced depression of phospho-NR1 expression.
IL-6 inhibits NMDA-stimulated neuronal firing activity, and simultaneously down-regulates the phosphorylation of NR1 at serine 897 site.
研究白细胞介素-6(IL-6)对体外培养的大鼠NMDA兴奋神经元放电的影响及其可能机制。
制备小脑切片,采用细胞外记录法记录单个小脑间位核(IN)神经元的自发放电。用含N-甲基-D-天冬氨酸(NMDA)、IL-6、JAK抑制剂AG490的人工脑脊液(ACSF)灌注小脑切片。记录药物处理后神经元放电活动的变化。采用蛋白质免疫印迹法检测上述各种药物处理后神经元中NMDA受体亚基1(NR1)丝氨酸897位点的磷酸化水平。
IL-6与NMDA共同处理的神经元放电率显著低于单独用NMDA处理的神经元。AG490部分阻断了IL-6对NMDA刺激的神经元放电活动的抑制作用。与单独用NMDA处理的神经元相比,IL-6和NMDA处理神经元导致磷酸化NR1表达呈浓度依赖性抑制。AG490阻断了IL-6诱导的磷酸化NR1表达降低的作用。
IL-6抑制NMDA刺激的神经元放电活动,同时下调NR1丝氨酸897位点的磷酸化。