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

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Author:
No author available
Journal Title:
ACTA PHYSIOLOGICA SINICA
Issue:
1
DOI:
10.3321/j.issn:0371-0874.2005.01.002
Key Word:
阿尔茨海默病;褪黑素;反式异丙肾上腺素;tau蛋白;异常磷酸化;Alzheimer's disease;melatonin;isoproterenol;tau;hyperphosphorylation

Abstract: Hyperphosphorylated microtubule-associated protein tau is the major protein component of neurofibrillary tangles in the brain of patients with Alzheimer's 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 d 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-l), and it was normalized by nonphosphorylation dependent total tau antibody (11 le). 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 Ser 396/Ser 404 (PHF-1) and Ser199/Ser 202 (Tau-1) sites. Similar results were observed by immunohistochemistry staining, in which hyperphosphorylated tau was mainly detected in mossy fibers of hippocampal CA3 region. Preinjection of rats with melatonin intraperitoneally arrested effectively the isoproterenol-induced tau hyperphosphorylation at both Tau1 and PHF-1 sites, implying the preventive effect of melatonin in Alzheimer-like tau hyperphosphorylation.

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