关键词: H102, APP/PS1双转基因小鼠, Morris水迷宫, Aβ_1-42

Abstract: Objective: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. 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 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_1-42) protein and phospho protein kinase C α、β₂、γ(p-PKCα, p-PKCβ₂, 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. 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 Aβ_1-42 proteins and p-PKCα, p-PKCβ₂, 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. Conclusion:β-sheet breaker peptide H102 can significantly improve synaptic plasticity and the ability of learning and memory in double transgenic AD mice.

Key words: H102, APP/PS1 double transgenic mice, Morris Water Maze, Aβ_1-42