Objective To investigate whether JNK-caspase-dependent apoptotic pathway is involved in Aβ31-35-induced apoptosis of cultured cortical neurons. Methods Cultured cortical neurons were treated with Aβ31-35 （25 μmol/L） for 4 h, 8 h, 16 h and 24 h, respectively. Caspase activities were measured using a spectrophotometer. Levels of c-Jun phosphorylation （p-c-Jun） and Fas ligand （FasL） expression were assessed by immunocytochemistry method and quantified using Image-pro plus11.0 image processing and analysis software. Results Treatment with Aβ31-35 （25 μmol/L） for 24 h induced significant increases in the activities of caspase-3 and caspase-8 in the cortical neurons. Besides, Aβ31-35 could time-dependently enhance the expression of p-c-Jun protein. Moreover, SP600125 application （100 nmol/L） could completely abolish Aβ31-35 neurotoxicity. The increase in FasL expression was detected at 8 h, 16 h and 24 h after Aβ31-35 treatment, and SP600125 （100 nmol/L） significantly inhibited FasL expression. Conclusion JNK-c-Jun-FasL-caspase-dependent extrinsic apoptotic pathway plays a critical role in mediating Aβ31-35-induced apoptosis of cultured neurons.
目的观察第Ⅲ组代谢型谷氨酸受体激动剂L-SOP和(R,S)-PPG对Aβ31～35所致培养神经元胞内Ca2+浓度升高的影响。方法原代培养的大鼠额叶皮层神经元,分别加入第Ⅲ组mG luR s激动剂L-SOP或(R,S)-PPG,利用实时Ca2+荧光成像技术观察对Aβ31～35所致〔Ca2+〕i升高的影响。结果急性给予Aβ31～35可引起培养神经元的〔Ca2+〕i水平呈剂量依赖性的升高,即随着Aβ31～35浓度的增加,其〔Ca2+〕i升高的幅度逐渐增加,而潜伏期逐渐缩短;经L-SOP或(R,S)-PPG预处理后,使Aβ31～35所引起的〔Ca2+〕i的平均升高幅度降低,平均潜伏期明显延长。结论在离体培养的神经元第Ⅲ组mG luR s的激活可通过抑制Aβ31～35引起的Ca2+超载,对Aβ31-35诱导的神经毒发挥保护作用。
