楮实子对APP/PS1双转基因小鼠海马神经发生的影响

Effects of Broussonetiae Fructus on hippocampal neurogenesis in double transgenic APP/PS1 mice

目的探讨楮实子对APP/PS1双转基因小鼠海马神经发生的影响。方法 40只APP/PS1双转基因小鼠随机分为模型组、阳性药组(10 mg/kg多奈哌齐)及楮实子低、高剂量组(1.8、3.6 g/kg),C57BL/6小鼠作为对照组,每组10只,灌胃给药6周。然后,Morris水迷宫实验检测小鼠学习记忆能力,TUNEL法检测小鼠海马区神经细胞凋亡,免疫荧光染色法检测小鼠海马区NeuN/BrdU阳性细胞表达,Western blot法检测GSK-3β、β-catenin蛋白表达。结果与模型组比较,楮实子高剂量组学习记忆能力显著改善(P<0.05),凋亡细胞数显著减少(P<0.01),NeuN/Brdu阳性细胞数显著增加(P<0.01),GSK-3β蛋白表达显著降低(P<0.05),β-catenin蛋白表达显著升高(P<0.05)。结论楮实子能促进APP/PS1双转基因小鼠海马神经发生,其机制可能与激活Wnt/β-catenin信号通路有关。

AIM To explore the effects of Broussonetiae Fructus on hippocampal neurogenesis in double transgenic APP / PS1 mice. METHODS Forty double transgenic APP / PS1 mice were randomly divided into model group, positive drug group (10 mg/ kg donepezil) and low-dose, high-dose Broussonetiae Fructus groups (1.8, 3.6 g/ kg), and C57BL/6 mice were recruited into control group, 10 mice in each group, and intragastric administration went on for 6 weeks. Subsequently, Morris water maze test was used to detect mouse learning and memory activities, TUNEL assay and immunofluorescence staining method were applied to detecting nerve cell apoptosis and NeuN/ BrdU positive cell expression in mouse hippocampal area, respectively, Western blot was adopted in the protein expression detection of GSK-3β and β-catenin. RESULTS Compared with the model group, the high-dose Broussonetiae Fructus group demonstrated significantly improved learning and memory activities ( P < 0.05), markedly reduced apoptosis cell count (P<0.01), obviously increased NeuN/ BrdU positive cell count (P<0.01), significantly decreased GSK-3β protein expression (P<0.05), and markedly elevated β-catenin protein expression (P<0.05). CONCLUSION Broussonetiae Fructus can promote hippocampal neurogenesis in double transgenic APP / PS1 mice, whose mechanisms may be related to the activation of Wnt/β-catenin signaling pathway.