中国病理生理杂志2016，Vol.32Issue(7)：1189-1194,6.DOI:10.3969/j.issn.1000-4718.2016.07.006
上调星形胶质细胞中PP2A对APP／PS1双转基因小鼠的神经保护作用
Neuroprotective effect of astrocyte protein phosphatase 2 A up-regulation on APP/PS1 double transgenic mice
摘要
Abstract
AIM:To investigate the protective effects of astrocyte protein phosphatase 2A (PP2A) up-regula-tion on APP/PS1 double transgenic mice.METHODS:An eGFP-wtPP2A lentivirus with glial fiber acidic protein promoter was constructed to specifically increase PP2A expression in the astrocytes.The mice were divided into wild -type mice +vector virus group (Con), APP/PS1 transgenic mice +vector virus group (APP/PS1) and APP/PS1 transgenic mice +eGFP-wtPP2A lentivirus group (PP2A) by lateral ventricular injection of the lentivirus.Four weeks after injection of the vi-rus, the immunofluorescence of brain slices were used to detect the level of β-amyloid protein ( Aβ) .Golgi staining was used to detect the changes of dendritic spine density and morphology.Electron microscopy was applied to detect the thickness of postsynaptic density (PSD).The Morris water maze test was applied to examine the learning and memory abilities of the mice.RESULTS: Up-regulation of PP2A in the astrocytes attenuated Aβlevel increasing in APP/PS1 group.Up-regulation of PP2A in the astrocytes significantly attenuated both decreases in the dendritic spine density and the percentage of mushroom-like dendritic spines in the hippocampal CA3 region of APP/PS1 mice.Up-regulation of PP2A in the astrocytes significantly attenuated the reduced thickness of PSD in APP/PS1 group.Up-regulation of PP2A in the astro-cytes attenuated the escape latency extending in APP/PS1 group .CONCLUSION: Up-regulation of PP2A in the astro-cytes reduces AD-like pathological changes, and attenuates synaptic impairment, synaptic plasticity deficits and cognitive impairment in the APP/PS1 double transgenic mice.关键词
蛋白磷酸酶2A/星形胶质细胞/APP/PS1 双转基因小鼠/神经保护作用Key words
Protein phosphatase 2A/Astrocytes/APP/PS1 double transgenic mice/Neuroprotective effect分类
临床医学引用本文复制引用
李夏春,彭敏峰,高丽华,楼正青,柳秀平..上调星形胶质细胞中PP2A对APP／PS1双转基因小鼠的神经保护作用[J].中国病理生理杂志,2016,32(7):1189-1194,6.基金项目
国家自然科学基金资助项目 （）
