褪黑素对异丙肾上腺素诱导的大鼠海马tau蛋白过度磷酸化和空间记忆损伤的保护作用

摘要

目的:在大鼠整体研究褪黑素对异丙肾上腺素(IP)诱导的tau过度磷酸化和动物保留记忆损伤的保护作用.方法:大鼠海马双侧注射IP或同时注射褪黑素(0.1 μg,1 μg),利用免疫组化、免疫印迹和Morris水迷宫等指标,观察褪黑素的效果.结果:0.1 μg和1 μg剂量的褪黑素明显降低IP引起的海马骨架蛋白Tau Ser396/404位点的过度磷酸化;1 μg褪黑素可明显改善IP引起的动物保留记忆损伤.结论:褪黑素对大鼠学习记忆和海马骨架蛋白Tau有一定的保护作用.%AIM: To study the in vivo effect of melatonin (MEL) on Alzheimer-like tau hyperphosphorylation and spatial memory retention impairment induced by isoproterenol (IP). METHODS: Simultaneous injection of 2 μL IP(10 mmol/L) or IP plus MEL(0.1 μg，1μg)into rat hippocampus bilaterally with stereotexin; The phosphorylation of tau was analyzed by immunohistochemistry and Western blot and the memory retention was tested by Morris Water Maze. RESULTS:Injection of IP induced hyperphosphorylation of tau at Tau-1 and PHF-1 epitopes and increased latency of rats to find the hidden platform in the Morris water maze. MEL significantly restored the IP-induced impairment in spatial memory(P＜0.05)and tau hyperphosphorylation determined by both immunocytochemistry and Western blot.CONCLUSION:MEL inhibits partially the IP-induced pathological processes in tau hyperphosphorylation and spatial memory impairment in rat brain.