Alzheimer-like tau phosphorylation induced by wortmannin in vivo and its attenuation by melatonin.
Alzheimer-like tau phosphorylation induced by wortmannin in vivo and its attenuation by melatonin.
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发表时间：
2002-02
影响因子：
8.2
通讯作者：
Shi-jie Liu;Jian-Zhi Wang
中科院分区：
文献类型：
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作者：
Shi-jie Liu;Jian-Zhi Wang
目的探讨沃特曼宁在体内诱导阿尔茨海默样tau蛋白磷酸化和褪黑素对其抑制作用。方法采用立体定向技术在大鼠侧脑室内给药沃曼宁或褪黑素。免疫细胞化学和Western blot检测tau蛋白磷酸化水平，电镜观察神经元过程超微结构变化。结果注射10 μ mol/L worwormannin后，配对螺旋丝-1 （PHF-1）表位磷酸化tau蛋白水平在1 h升高，6 h达到峰值，12 h和24 h下降。6 h时测定的特定表位的tau磷酸化增加，通过10 μ mol/L或100 μ mol/L的褪黑素预注射12 h来抑制。wortmannin诱导的tau过度磷酸化主要在海马锥体神经元中检测到，在大脑的同一区域也可见到轴突肿胀和髓鞘退化。结论Wortmannin可诱导体内样阿尔茨海默病tau蛋白Ser396/404位点的过度磷酸化，褪黑素可部分抑制这一病理过程。
AIM To investigate the in vivo induction of Alzheimer-like tau phosphorylation by wortmannin and the attenuation by melatonin. METHODS Stereotaxic technique was used for administrating wortmannin or melatonin into rat lateral ventricle. The phosphorylation of tau was analyzed by immunocytochemistry and Western blot, and ultrastructural alteration in neuronal processes was detected by electron microscopy. RESULTS Level of phosphorylated tau at paired helical filament-1 (PHF-1) epitope was elevated at 1 h, peaked at 6 h, and then decreased at 12 h and 24 h after injection of wortmannin 10 mumol/L. The increased tau phosphorylation at particular epitope determined at 6 h was arrested by preinjection of melatonin 10 mumol/L or 100 mumol/L for 12 h. The wortmannin-induced hyperphosphorylation of tau was mainly detected in pyramidal neuron of hippocampus, and swelled axons and depredated myelin sheaths were also seen in the same region of the brain. CONCLUSION Wortmannin induced in vivo Alzheimer-like hyperphosphorylation of tau at Ser396/404, and melatonin inhibited partially the pathological processes.