Effects of β-sheet breaker peptide H102 on synaptic plasticity associated proteins in double transgenic AD mice

Abstract

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 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(Aβ1-42) 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. 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-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.