Alzheimer-like tau phosphorylation induced by wortmannin in vivo and its attenuation by melatonin.
OBJECTIVE
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.


CONCLUSIONS
Wortmannin induced in vivo Alzheimer-like hyperphosphorylation of tau at Ser396/404, and melatonin inhibited partially the pathological processes.
Liu
Shi-Jie
SJ
Department of Pathophysiology, Tongji Medical College, Huazhong Science and Technical University, Wuhan 430030, China.
Wang
Jian-Zhi
JZ
D000544:Alzheimer Disease / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D016874:Neurofibrillary Tangles / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology; D000077191:Wortmannin; D016875:tau Proteins / Q000378:metabolism*
D000730:Androstadienes; D000975:Antioxidants; D012702:Serotonin Antagonists; D016875:tau Proteins; D008550:Melatonin; D000077191:Wortmannin