Wnt/β-catenin pathway regulating glucocorticoids-mediated Alzheimer’s disease-like pathological changes

Objective To investigate the role of Wnt/β-catenin pathway in the glucocorticoids(GC)-mediated Alzheimer’s disease-like pathological changes in vitro. Methods Human embryonic kidney 293 (HEK293/wt) cells stably transfected with the longest human tau (tau441,HEK293/tau) and wild-type HEK293 cells were employed to study the role of GC. Cell viabilities of the two cell lines were examined by cell counting kit-8（CCK-8）. Levels of phosphorylated tau (p-T205) and dephosphorylated tau (Tau-1), β-catenin, phosphorylated β-catenin (p-β-catenin), glycogen synthase kinase-3β (GSK-3β), phosphorylated GSK-3β at Ser9 (ps9-GSK-3β) and Bcl-2 were determined by Western blotting. Results Treatment with 1 μmol/L GC for 48 h decreased the viability of HEK293/wt and HEK293/tau cells to 95.5%±3.2% and 77.8%±4.4% (t=6.60, P<0.05). Moreover, GC treatment decreased the levels of ps9-GSK3β, Tau-1, β-catenin and Bcl-2 to 47.8%±10.4%, 53.9%±11.7%, 50.9%±7.6%, 48.4%±6.5% of control groups (t=7.01，3.86，7.09，7.30, all P<0.05), and increased the relative levels of pT205, p-β-catenin to 180.5%±22.2%, 201.3%±27.6% of control groups (t=5.51，5.27, both P<0.05) only in HEK293/tau cells. Finally, LiCl efficiently prevented the above effects of GC in HEK293/tau cells. Conclusion GC may trigger Alzheimer’s disease-like pathological changes by inhibiting the Wnt/β-catenin pathway and these pathological processes seem to specifically depend on the presence of human tau. Key words: Alzheimer disease; beta Catenin; tau Proteins; Dexamethasone; Glycogen synthase kinase 3