摘要
目的:观察β片层阻断肽H102对双转基因AD小鼠突触可塑性相关蛋白表达及学习记忆能力的影响,探讨H102的作用机制。方法:选用8周龄APPswe/PS1dE9双转基因雄性小鼠30只,随机选取15只小鼠设为模型组,剩下15只小鼠设为给药组;对照组选用15只同周龄同背景C57BL/6J小鼠。给药组每日经鼻腔给予H102溶液(5.8mg/kg)5μl,对照组和模型组每日经鼻腔给予辅料溶液5μl。给药16周后,采用Morris水迷宫法检测双转基因AD小鼠空间学习记忆能力的变化,采用免疫组织化学方法和Western blot实验技术测定β-淀粉样蛋白1-42(Aβ_(1-42))和突触可塑性相关蛋白磷酸化蛋白激酶C亚型α、β_2、γ(p-PKCα、p-PKCβ_2、p-PKCγ)、磷酸化离子型谷氨酸受体1(pNMDARI)、磷酸化钙/钙调素依赖蛋白激酶α(p-CaMKIIα)和磷酸化环腺苷酸应答元件结合蛋白(p-CREB)在小鼠脑中的表达水平。结果:Morris水迷宫检测结果表明H102能明显提高双转基因AD小鼠的空间学习记忆的能力。免疫组织化学和Western blot技术检测表明H102能明显减少双转基因AD小鼠脑内Aβ_(1-42)蛋白的表达,H102能明显提高双转基因AD小鼠脑内突触可塑性相关蛋白p-PKCα、p-PKCβ_2、p-PKCγ、p-NMDAR1、p-CaMKIIα和p-CREB的表达。结论:β片层阻断肽H102能提高双转基因AD小鼠的突触可塑性,提高双转基因AD小鼠的学习记忆能力。
Objective： To investigate the effects of β-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. Methods： 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 μl was infused by intranasal administration to mice in H102 treatment group, and equal volume of blank solution of H102 （chitosan, BSA） was given to mice in control group and model group. The ability of spatial reference memory was tested by Morris Water Maze after 16 weeks treatment, then immunohistochemistry tests and Western blot technique were used to detect the content of β-amyloid peptide（ Aβ1-42 ） protein and phospho protein kinase C α,β2,γ（p-PKCα, p-PKCβ2, p-PKCγ）, phospho-N-methyl-D-aspartate receptorl（p-NMDARl）, phospbo-Calcium/Calmodulin dependent protein kinaseⅡ α（p-CaMKⅡα） and phospho-cAMP response element binding protein（p-CREB） of synaptic plasticity associated proteins in mice brain. Results： 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 Aβ1-42 proteins and p-PKCα, p-PKCβ2, p-PKCγ, p-NMDARγ, p-CaMKⅡα and p-CREB of synaptic plasticity associated proteins in mice brain were improved significantly in HI02 treatment group than those in model group by the test of immunohistochemistry tests and Western blot technique. Conclusion： β-sheet breaker peptide H102 can significantly improve synaptic plasticity and the ability of learning and memory in double transgenic AD mice.
出处
《中国应用生理学杂志》
CAS
CSCD
2016年第4期293-298,I0004,共7页
Chinese Journal of Applied Physiology
基金
国家科技重大专项基金资助(2009ZX09103029)
天津市科技支撑重点项目基金资助(09ZCKFSH00100)
