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Prevention of isoproterenol-induced tau hyperphosphorylation by melatonin in the rat

Wang Xiaochuan, Zhang Jing, Yu Xian, Han Liu, Zhou Zhentao, Zhang Yao, Wang Jianzhi

Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology.Wuhan 430030,Hubei

Abstract

Hyperphosphorylated microtubule-associated protein tau is the major protein component of neurofibrillary tangles in the brain of patients with Alzheimer disease (AD). Until now, there is no effective cure to arrest this hyperphosphorylation. The present study was designed to explore the in vivo preventive effect of melatonin on Alzheimer-like tau hyperphosphorylation. Isoproterenol, a β-receptor agonist, was used to induce tau hyperphosphorylation, and for preventive effect of melatonin, the rats were injected intraperitoneally with melatonin for 5 days before hippocampi infusion of isoproterenol. The level of tau phosphorylation was detected by Western blot and immunohistochemistry using sites specific antibodies (PHF-1 and Tau-1), and it was normalized by non-phosphorylation dependent total tau antibody (111e). The results by Western blot showed that the immunoreaction of tau at PHF-1 epitope was enhanced, and the reaction at Tau-1 epitope was weakened significantly at 48 h after injection of isoproterenol, suggesting hyperphosphorylation of tau at Ser396/Ser404 (PHF-1) and Ser199/Ser202 (Tau-1) sites. Similar results were observed by immunohistochemistry staining, in which hyperphosphorylated tau was mainly detected in mossy fibers of hippocampal CA3 region. Pre-injection of rats with melatonin intraperitoneally arrested effectively the isoproterenol-induced tau hyperphosphorylation at both Tau-1 and PHF-1 sites, implying the preventive effect of melatonin in Alzheimer-like tau hyperphosphorylation.

Key words: Alzheimer disease's;Melatonin;Isoproterenol;Tau;Hyperphosphorylation

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Citing This Article：

Wang Xiaochuan, Zhang Jing, Yu Xian, Han Liu, Zhou Zhentao, Zhang Yao, Wang Jianzhi. Prevention of isoproterenol-induced tau hyperphosphorylation by melatonin in the rat. Acta Physiol Sin 2005; 57 (1): (in Chinese with English abstract).