Journal of Neural Transmission

, Volume 113, Issue 11, pp 1803–1814

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

  • S. Yoshida
  • M. Maeda
  • S. Kaku
  • H. Ikeya
  • K. Yamada
  • S. Nakaike
Article

DOI: 10.1007/s00702-006-0528-0

Cite this article as:
Yoshida, S., Maeda, M., Kaku, S. et al. J Neural Transm (2006) 113: 1803. doi:10.1007/s00702-006-0528-0

Summary.

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.

Keywords: Stress, tau phosphorylation, GSK-3β, lithium 

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • S. Yoshida
    • 1
    • 4
  • M. Maeda
    • 1
  • S. Kaku
    • 2
  • H. Ikeya
    • 3
  • K. Yamada
    • 4
  • S. Nakaike
    • 1
  1. 1.Pharmacology Laboratory, Medicinal Research LaboratoriesTaisho Pharmaceutical Co., LTD.SaitamJapan
  2. 2.Medicinal Pharmacology Laboratory, Medicinal Research LaboratoriesTaisho Pharmaceutical Co., LTDSaitamJapan
  3. 3.Lead Generation Laboratory, Medicinal Research LaboratoriesTaisho Pharmaceutical Co., LTD.SaitamJapan
  4. 4.Laboratory of NeuropsychopharmacologyKanazawa University Graduate School of Natural Science & TechnologyKakuma-machiJapan