Effects of Valproic Acid Combined with 17β-Estradiol on Mental Behavior and Neurons in Ovariectomized APP/PS1 Double Transgenic Mice
Li Yanzhen, Zhang Wei, Jiang Tingting, Luo Min, Du Yexiang, He Guiqiong, Luo Shifang*
The aim of this study was to investigate the effects of valproic acid (VPA) and 17β-Estradiol (E2) on mental behavior and neurons in ovariectomized APP/PS1 double transgenic mice. The 3.5-month-old female APP/PS1 double transgenic mice underwent bilateral ovariectomy (OVX). After one month, the mice were randomly divided into 4 groups, and then treated with VPA and E2 alone or in combination for one month (Saline group as control). The results of the elevated plus maze test showed that compared with the control group, the number of VPA group and E2 group mice entering the open arm and the open arm stagnation time increased, but there was no statistical significance (P>0.05), while the VPA+E2 group showed a significant increase compared with the control group (P<0.05). The results of open field experiments showed that compared with the control group, the distance and time of activity in the central area of the drug treatment groups were significantly upregulated (P<0.05), which could significantly improve the anxiety and autonomic activity of mice. Compared with the control group, the expression of NeuN in E2 group and VPA+E2 group was statistically significant (P<0.05), and there was no significant change in VPA group (P>0.05). Golgi staining showed that the dendritic spine density in the VPA+E2 group was significantly higher than that in the control group and the E2 group (P<0.05), which was 1.39 times higher than that in the VPA group, but there was no statistically significant difference (P>0.05). Western blot showed that the expression of ERα in E2 group and VPA+E2 group was significantly higher than that in the control group (P<0.05), and the VPA+E2 group was more significant. There was no significant difference (P>0.05) between VPA group and control group. The expression of Wnt3a in the brain of VPA+E2 group was significantly higher than that of the control group, VPA group and E2 group (P<0.05). The content of β-Catenin in E2 group and VPA+E2 group compared with the control group was statistically significant (P<0.05). These results indicate that sodium valproate combined with 17β-Estradiol can alleviate the anxiety of mice and delay the degeneration of neurons in the brain of mice, which may be related to the activation of ERα-Wnt/β-Catenin signaling pathway.
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