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Aβ31～3...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。展开更多
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/...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.展开更多
文摘目的观察第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。
基金supported by the Special Foundation for High Schools Doctoral Program of Ministry of EducationChina (No.20101417110001)+5 种基金the Scientific Research Foundation for the Returned Overseas Chinese Scholars in Shanxi ProvinceChina (No.2010-51)the Natural Science Foundation of Shanxi Province of China (No.2010011049-3)Science and Technology Fund of Taiyuan Municipality (No.201010-1400)Scientific and Technologial Innovation Programs of Higher Education Institutions in Shanxi ProvinceChina (No.20091111)
基金supported by the National Natural Science Foundation of China (No. 30572085)Natural Science Foundation of Shanxi Province, China(No. 2007011111)
文摘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.
