Yuan Xiao-Yong, Wang Chao, Sun Feng-Xian, Xu Shu-Mei
Department of Physiology, Tianjin Medical University, Tianjin 300070, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2016 Apr 8;32(4):293-298. doi: 10.13459/j.cnki.cjap.2016.04.002.
To investigate the effects ofβ-sheet breaker peptide H102 on expression of synaptic plasticity associated proteins and learning and memory functions in double transgenic Alzheimer's disease(AD) mice,and to discuss its mechanisms.
Thirty APP-swe/PS1dE9 double transgenic male mice of 8 weeks were randomly divided into model group and H102 treatment group (15 mice per group). In addition,a group of C57BL/6J mice with the same age and background was set as normal. H102 (5.8 mg/kg) 5 l was infused by in-tranasal administration to mice in H102 treatment group,and equal volume of blank solution of H102 (chitosan,BSA) was given to mice in con-trol group and model group. The ability of spatial reference memory was tested by Morris Water Maze after 16 weeks treatment,then immunohis-tochemistry tests and Western blot technique were used to detect the content ofβ-amyloid peptide(Aβ) protein and phospho protein kinase C α、β、γ(p-PKCα, p-PKCβ, p-PKCγ), phospho-N-methyl-D-aspartate receptor1(p-NMDAR1), phospho-Calcium/Calmodulin dependent pro-tein kinaseⅡα(p-CaMKⅡα) and phospho-cAMP response element binding protein(p-CREB) of synaptic plasticity associated proteins in mice brain.
The ability of learning and memory was significantly improved in H102 treatment group than that in model group by the test of Morris Water Maze. The contents of Aβ proteins and p-PKCα, p-PKCβ, p-PKCγ, p-NMDAR1, p-CaMKⅡαand p-CREB of synaptic plas-ticity associated proteins in mice brain were improved significantly in H102 treatment group than those in model group by the test of immunohis-tochemistry tests and Western blot technique.
β-sheet breaker peptide H102 can significantly improve synaptic plasticity and the ability of learning and memory in double transgenic AD mice.
探讨β-折叠破坏肽H102对双转基因阿尔茨海默病（AD）小鼠突触可塑性相关蛋白表达及学习记忆功能的影响，并探讨其作用机制。
将30只8周龄的APP-swe/PS1dE9双转基因雄性小鼠随机分为模型组和H102治疗组（每组15只）。另外，设一组同龄同背景的C57BL/6J小鼠作为正常对照组。对H102治疗组小鼠采用鼻腔给药法注入5 μl H102（5.8 mg/kg），对照组和模型组小鼠给予等量的H102空白溶液（壳聚糖、牛血清白蛋白）。治疗16周后，采用Morris水迷宫检测空间参考记忆能力，然后用免疫组织化学检测和蛋白质印迹技术检测小鼠脑内β-淀粉样肽（Aβ）蛋白及突触可塑性相关蛋白磷酸化蛋白激酶Cα、β、γ（p-PKCα、p-PKCβ、p-PKCγ）、磷酸化N-甲基-D-天冬氨酸受体1（p-NMDAR1）、磷酸化钙/钙调蛋白依赖性蛋白激酶Ⅱα（p-CaMKⅡα）和磷酸化环磷腺苷反应元件结合蛋白（p-CREB）的含量。
通过Morris水迷宫检测发现，H102治疗组小鼠的学习记忆能力较模型组显著提高。通过免疫组织化学检测和蛋白质印迹技术检测发现，H102治疗组小鼠脑内Aβ蛋白及突触可塑性相关蛋白p-PKCα、p-PKCβ、p-PKCγ、p-NMDAR1、p-CaMKⅡα和p-CREB的含量较模型组显著提高。
β-折叠破坏肽H102可显著改善双转基因AD小鼠的突触可塑性及学习记忆能力。
