老年痴呆症模型小鼠蛋白磷酸化与短期丰富环境刺激的影响  

Short-term environmental enrichment stimulation influences protein phosphorylation of Alzheimer's disease transgenic mice

作　　者：黄娴[1] 张凌[1] 李雪[1] 

机构地区：[1]清华大学医学院学习与记忆研究中心,北京市100084

出　　处：《中国组织工程研究与临床康复》2012年第2期269-272,共4页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：国家973项目(2011CB302201)~~

摘　　要：背景:丰富环境刺激可提高对神经可塑性、学习记忆很重要的CAMKII、CREB蛋白的转录。目的:探讨短期丰富环境刺激对老年痴呆模型小鼠海马CAMKII和CREB蛋白磷酸化的影响。方法:实验分3组:长期环境组(以APP/PS1转基因C57/BL6小鼠作为老年痴呆症动物模型,从小鼠6月龄时开始进行长期的丰富环境刺激)、对照组(未进行长期环境刺激的APP/PS1转基因C57/BL6小鼠)与野生型组(非转基因的野生型C57/BL6小鼠)。在3组小鼠18月龄时,每组又随机分为基线组和刺激后两个亚组,对刺激后亚组施以为期1d的短期丰富环境刺激。结果与结论:野生型组的刺激后亚组海马CREB磷酸化水平显著高于基线亚组(P<0.05),CAMKII的磷酸化水平也有所升高;丰富环境组的刺激后亚组海马CAMKII磷酸化水平稍高于基线亚组,CREB磷酸化水平的区别不明显;对照组两个亚组海马的CAMKII和CREB磷酸化水平无明显区别。说明短期丰富环境刺激仅提高了丰富环境刺激后老年痴呆症小鼠的CAMKII磷酸化水平,但显著提高了野生型小鼠的CAMKII和CREB磷酸化水平。BACKGROUND： Long-term environmental enrichment （EE） stimulation can enhance the transcription of CAMKII and CREB which are very important proteins for neuronal plasticity, learning and memory. OBJECTIVE： To explore the effects of short-term environmental enrichment stimulation on phosphorylation of CAMKII and CREB in Alzheimer＇s disease mice. METHODS： Either C57/BL6 mice （wild type） or APP/PS1 transgenic mice were used. These laboratorial mice were assigned into three groups： APP/PS1＋EE group （ long-term EE stimulations were performed when APP/PS1 transgenic mice, as Alzheimer＇s disease models, were 6 months old）, APP/PS1 control group （APP/PS1 transgenic mice without long-term EE stimulations） and wild-type group （wild type C57/BL6 mice）. When the mice of the 3 groups reached to 18 months, each group was randomly divided into two subgroups, baseline subgroup and stimulation subgroup. The mice in every stimulation subgroup were treated with 1 day （short-term） EE stimulation. RESULTS AND CONCLUSION： In the wild type group, the CREB phosphorylation level in the stimulation subgroup was significantly higher than that in the baseline subgroup （P 0.05）, and the CAMKII phosphorylation level had also increased. In the APP/PS1＋EE group, the CAMKII phosphorylation level in the stimulation subgroup was slightly higher than that in the baseline subgroup, and there was no distinct difference in the CREB phosphorylation level between the two subgroups. In the APP/PS1 control group, there was no significant difference in CAMKII and CREB phosphorylation levels between the two subgroups. These findings suggest that short-term EE stimulation can induce an increase of CAMKII phosphorylation level in Alzheimer＇s disease mice only after long-term EE stimulation. However, it can obviously improve the phosphorylation level of CAMKII and CREB in wild type mice.

关 键 词：老年痴呆症 短期 长期 丰富环境 海马 蛋白磷酸化 

分 类 号：R318[医药卫生—生物医学工程]