摘要
该文旨在研究丙戊酸钠(valproic acid, VPA)和雌二醇(17β-Estradiol, E2)联合用药对去卵巢APP/PS1双转基因小鼠精神行为和脑内神经元的影响及可能机制。将3.5月龄雌性APP/PS1双转基因小鼠进行双侧卵巢切除(ovariectomy, OVX), 1个月后随机将小鼠分为4组,然后单独或联合应用VPA和E2处理1个月(生理盐水组为对照)。高架十字迷宫实验结果显示,与对照组相比, VPA和E2单独用药组小鼠进入开放臂的次数和在开臂停滞时间均有上升,但无统计学意义(P>0.05),而VPA+E2联合用药组小鼠较对照组有显著上升(P<0.05)。旷场实验结果显示,与对照组相比,各药物处理组小鼠在旷场中央区活动的路程和时间显著上调(P<0.05),这可显著改善小鼠的焦虑情绪和自主性活动变化。与对照组相比, E2组和VPA+E2组NeuN的表达量升高具有统计学意义(P<0.05),VPA组无明显改变(P>0.05);高尔基染色结果显示, VPA+E2组树突棘密度升高较对照组和E2组均具有统计学意义(P<0.05),是VPA组的1.39倍,但无显著统计学差异(P>0.05)。Western blot结果显示, E2组和VPA+E2组与对照组相比ERα的表达量升高具有统计学差异(P<0.05),其中VPA+E2组升高更为显著, VPA组与对照组相比没有明显差异(P>0.05);VPA+E2组小鼠脑内Wnt3a表达量与对照组、VPA组和E2组相比其升高均具有统计学意义(P<0.05);E2组和VPA+E2组β-Catenin含量相较对照组升高具有显著统计学意义(P<0.05)。上述结果说明,丙戊酸钠联合雌二醇治疗可缓解小鼠的焦虑情绪并延缓小鼠脑内神经元的变性,这种改善作用可能与ERα-Wnt/β-Catenin信号通路激活相关。
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 ERαin 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 Wnt3 a 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 ofβ-Catenin in E2 group and VPA+E2 group compared with the control group was statistically significant(P<0.05).These results indicate tha
作者
李彦臻
张威
姜婷婷
罗敏
杜烨湘
贺桂琼
骆世芳
Li Yanzhen;Zhang Wei;Jiang Tingting;Luo Min;Du Yexiang;He Guiqiong;Luo Shifang(Chongqing Medical University Neuroscience Research Center,Chongqing 400016,China)
出处
《中国细胞生物学学报》
CAS
CSCD
2019年第4期660-667,共8页
Chinese Journal of Cell Biology
基金
国家自然科学基金(批准号:81671257、81371221)
重庆市基础与前沿研究计划项目(批准号:cstc2016jcyjA0069)资助的课题~~
关键词
阿尔茨海默病
焦虑
神经元
丙戊酸钠
雌激素
Alzheimer’s disease
anxiety
neurons
valproate acid
17β-Estradiol
