Alzheimer-like tau phosphorylation induced by wortmannin in vivo and its attenuation by melatonin.
Abstract
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.
Keywords:
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.