Lithium inhibits stress-induced changes in tau phosphorylation in the mouse hippocampus

S. Yoshida, M. Maeda, S. Kaku, H. Ikeya, K. Yamada, S. Nakaike

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22 Citations (Scopus)

Abstract

It has been pointed out that hyperphosphorylation of microtubule-associated protein tau caused by stress might participate in the early stages of Alzheimer's disease pathogenesis. In the present study, we investigated the effects of cold water stress (CWS) on tau phosphorylation in the mouse hippocampus and the effects of GSK-3β inhibitor, LiCl, on CWS-induced changes in tau phosphorylation levels by immunoblot analyses. CWS exposure caused an increase in tau phosphorylation at the Tau-1 (Ser199/202), AT8 (Ser202/Thr205) and Ser396 sites. CWS-induced changes in tau phosphorylation at the Ser199/202 and Ser396, but not at Ser202/Thr205, were significantly attenuated by LiCl pretreatment. Total tau levels also showed a decided tendency to increase after CWS, which tendency was also countered by LiCl. Finally, we showed that CWS increased the active form of GSK-3β that was phosphorylated at Tyr216. These results suggest that a CWS-induced increase in phosphorylated tau in the hippocampus is mediated, at least partly, by the activation of GSK-3β.

Original languageEnglish
Pages (from-to)1803-1814
Number of pages12
JournalJournal of Neural Transmission
Volume113
Issue number11
DOIs
Publication statusPublished - 11-2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

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