Objective      To investigate the effect of sodium valproate (VPA) on the hyperphosphorylation of Tau (p-Tau-Ser262) and neurofibrillary tangles (NFTs) in the brain tissues of APP/PS1 double transgenic mouse models of Alzheimer’s disease (AD).       Methods      Twenty APP/PS1 transgenic mice (3 months old) were randomly divided into a control group and a VPA group (10 mice in each group). The mice of the VPA group and the control group were intraperitoneally injected with VPA and the same amount of normal saline once a day for 4 weeks

respectively. Immunohistochemical staining was applied to detect the number of p-Tau-Ser262-positive cells

and HE staining was applied to observe the number and distribution of NFTs in the brain tissues of the AD mice. The level of phospho-glycogen synthase kinase 3β-Ser9 (p-GSK-3β-Ser9) in the brain tissues of AD mice was analyzed by Western blotting.       Results      The result of immunohistochemical staining showed that the number of p-Tau-Ser262-positive cells was significantly lower in the cerebral cortex (5.01±0.71)

hippocampus (5.29±1.32)

olfactory bulb (10.06±3.36) and cerebellum (13.54±1.51) of the VPA group as compared with those of the control group (8.60±1.82

9.00±1.87

56.00±6.67 and 22.02±1.98

P0.05

P0.01). The HE staining result revealed that the number of NFTs significantly decreased in the hippocampus (1.33±0.71) and cerebral cortex (1.90±0.88) of the VPA group as compared with those of the control group (5.89±0.92 and 6.08±1.61

P0.01). Western blotting results showed that the level of p-GSK-3β-Ser9 in the brain tissues of the VPA group was significantly higher than those of the control group (126.88±5.61 vs 73.34±3.61

P0.01).       Conclusion      VPA can significantly inhibit the hyperphosphorylation of Tau and the formation of NFTs in the brain tissues of APP/PS1 double transgenic mice through downregulating the activity of GSK-3β.