DAIa2-GIP-GIu-PAL To APP / PS1 Transgenic Alzheimer Disease Mouse Model Of Spatial Learning And Memory Functions

[Abstract] Type2diabetes has been considered as a risk factor for Alzheimer’s disease (AD). insulin signal damaged and insulin receptor desensitization phenomenon has been found in AD brains. Glucose-dependent insulinotropic polypeptide (GIP) and its analogues of insulin by promoting the release of insulin to make insulin signal back to normal. GIP directly regulate the neurotransmitter release, LTP formation, and protection from β amyloid protein fragments in LTP formation, cell proliferation and progenitor cells in the hippocampal dentate gyrus of harmful effects.Objective: This research adopts the Morris Water Maze behavior experiment technology, Here we investigate a new long lasting GIP analogue D-Ala2-GIP-Glu-PAL of Alzheimer’ disease mouse model (APP/PS1) the influence of Spatial learning and memory function. Provide a basis for further study on the AD treatment.Methods:D-Ala2-GIP-GLU-PAL was injected for60days at25nmol/kg ip once daily in APP/PS1male mice and wild type (WT) littermates aged6months of age which was also male mice. The control group, with0.9%of the saline intraperitoneal injection of10ml/kg quantity once daily. And after then we can do the Behavioral test,which is Morris Water Maze test. The main measures include:the escape incubation period of Mice to search for underwater navigation test platform for5days, escape distance; Space exploration test after removal the platform, The Percentage of target quadrant swimming time and distance,The number of Through the platform and the first quadrant.Results:Compared with normal saline group, Drug treatment group escape latency and escape range reduced (P<0.01),The percentage of Target quadrant swimming time and distance increase (P<0.01),The Number of Through the platform and the first quadrant is increase (P <0.01).Conclusions:Through the drug of D-Ala2-GIP-GLU-PAL’s therapy, Not only can improve the spatial learning and memory ability on APP/PS1mice, but also to the Normal mice the spatial learning and memory ability have increase, It shows that this new type of GIP analogues as a new drug possibility for the treatment of AD.