丰富环境对慢性睡眠剥夺小鼠大脑皮层和海马Aβ1-42及相关代谢分子BACE1的影响

Effects of environmental enrichment on Aβ1-42 and related metabolic molecule BACE1 in prefrontal cortex and hippocampus of chronic sleep-deprived mice

目的:探讨丰富环境(enriched environment, EE)对慢性睡眠剥夺小鼠前额叶皮层和海马Aβ1-42及相关代谢分子β位点淀粉样前体蛋白裂解酶1(β-site amyloid precursor protein cleaving enzyme 1, BACE1)表达的影响。方法:3月龄SPF级健康雄性昆明小鼠40只,体重21~25 g,随机分为4组:标准环境对照(control, Ctrl)组、睡眠剥夺(sleep deprivation, SD)组、EE组和SD+EE组。采用改良的多平台睡眠剥夺模型建模,每天干预19 h,EE组及SD+EE组分别每天进行8 h EE干预。采用Y迷宫法及新物体识别对小鼠进行行为学分析;免疫荧光法检测小鼠前额叶皮层与海马Aβ1-42沉积情况;Western blot法检测前额叶皮层和海马组织中BACE1蛋白的表达水平。结果:与Ctrl组小鼠相比,SD组小鼠学习记忆功能和认知功能减退(P<0.01),前额叶皮层及海马Aβ1-42和BACE1蛋白的表达均有不同程度的升高(P<0.01);EE组小鼠学习记忆功能和认知功能提高(P<0.01),前额叶皮层及海马Aβ1-42表达均减少(P<0.05),前额叶皮层BACE1蛋白在两组间的差异无统计学意义(P>0.05),但海马BACE1蛋白的表达较Ctrl组减少(P<0.01)。与SD组相比,SD+EE组小鼠学习记忆功能和认知功能改善(P<0.01),前额叶皮层和海马Aβ1-42和BACE1蛋白表达均减少(P<0.01)。结论:丰富环境可以减少慢性睡眠剥夺小鼠前额叶皮层和海马Aβ1-42的沉积及BACE1蛋白的表达,同时改善慢性睡眠剥夺小鼠的学习记忆功能以及认知功能。

AIM:To investigate the effects of environmental enrichment(EE) on Aβ1-42 and related metabolic molecule β-site amyloid precursor protein cleaving enzyme 1(BACE1) in the prefrontal cortex and hippocampus of chronic sleep deprivation mice. METHODS:Forty 3-month-old SPF-grade healthy male Kunming mice, weighing 21~25g, were randomly divided into 4 groups:standard environment control(Ctrl) group, sleep deprivation(SD) group, EE group and SD+EE group. A modified multi-platform sleep deprivation model was used for 19 hours per day. 8 hours per day of EE intervention was performed in the EE group and SD+EE group, respectively. The behavioral measurements of mice were performed by the Y-maze method and new object recognition. The immunofluorescence method was used to determine the deposition of Aβ1-42 in mouse prefrontal cortex and hippocampus. BACE1 protein expression levels in the prefrontal cortex and hippocampus by detected by Western blot. RESULTS:Compared with the Ctrl group, the SD group mice showed decreased learning and memory function and cognitive function(P<0. 01), increased expression of Aβ1-42and BACE1 in the prefrontal cortex and hippocampus(P<0. 01). In the EE group, the learning and memory function and cognitive function were improved(P<0. 01), and the expression of Aβ1-42 in the prefrontal cortex and hippocampus was decreased(P <0. 05),there was no significant difference in BACE1 protein expression in the prefrontal cortex(P>0. 05), but the expression of BACE1 protein in the hippocampus was decreased compared with Ctrl group(P<0. 01). Compared with the SD group, the SD+EE group showed improved learning and memory function and cognitive function(P<0. 01), decreased expression of Aβ1-42 and BACE1 protein in the prefrontal cortex and hippocampus(P<0. 01). CONCLUSION:EE can reduce the deposition of Aβ1-42 and the expression of BACE1 protein in the prefrontal cortex and hippocampus of chronic sleep-deprived mice, and improve the learning and memory function and cognitive function of chronic sleep-deprived mice.