Journal of Neural Transmission

, Volume 113, Issue 1, pp 93–102 | Cite as

Activation of glycogen synthase kinase-3 induces Alzheimer-like tau hyperphosphorylation in rat hippocampus slices in culture

  • X. Li
  • F. Lu
  • Q. Tian
  • Y. Yang
  • Q. Wang
  • J.-Z. Wang
Article
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Accepted:

Summary.

Formation of neurofibrillary tangle from hyperphosphorylated tau is one of the hallmark lesions seen in Alzheimer’s disease (AD) brain, and neuronal deregulation of glycogen synthase kinase-3 (GSK-3) activity plays key role in tau hyperphosphorylation. In the present study, the role of GSK-3 on tau phosphorylation in hippocampus slice culture was examined by incubating the slice with wortmannin (WT), an inhibitor of phosphatidylinositol 3-kinase (PI3K) and GF-109203X (GFX), an inhibitor of protein kinase C (PKC). It was found that treatment of the slices with GFX or WT separately induced tau hyperphosphorylation both at Ser396/Ser404 (PHF-1) and Ser199/Ser202 (Tau-1) sites. The phosphorylation rate of tau at PHF-1 and Tau-1 epitopes was further increased when GFX and WT were used in combination, and at this condition, AD-like tau accumulation was observed. GSK-3 activity was significantly increased with a concurrently decreased level of inactivated form of GSK-3. Lithium chloride (LiCl), a GSK-3 inhibitor, prevented tau from WT- and GFX-induced hyperphosphorylation. It suggests that GSK-3 is regulated through PI3K and PKC pathway, and activation of GSK-3 not only induces hyperphosphorylation of tau but also leads to accumulation of tau in cultured rat brain slice.

Keywords: Alzheimer’s disease, hyperphosphorylation, GSK-3, wortmannin, GF-109203X, LiCl. 
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Copyright information

© Springer-Verlag/Wien 2005

Authors and Affiliations

  • X. Li
    • 1
  • F. Lu
    • 1
  • Q. Tian
    • 1
  • Y. Yang
    • 1
  • Q. Wang
    • 1
  • J.-Z. Wang
    • 1
  1. 1.Pathophysiology DepartmentTongji Medical College, HuaZhong University of Science and TechnologyWuhanP.R. China

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