gw9508 and Cognition-Disorders

GPR40 was utilized as the drug target to the treatment of diabetes, but the function and mechanisms ameliorating the Alzheimer's disease (AD) remain unknown. In present study, the typical APP/PS1 mouse model was applied to explore the function and mechanism of GPR40 in AD. GPR40 agonist GW9508 and antagonist GW1100 were respectively given by i.c.v. injection to activate/inhibit the GPR40 in the brain of APP/PS1 mice which illustrated the function and mechanism of GPR40 in ameliorating AD symptoms. Morris water maze test, step-through test, Y-maze spontaneous alternation test, open field test and new object recognition test were used to test the cognitive function and memory ability of mice, while molecular biology experiments such as Western blot, immunofluorescence, JC-1 were used to detect the corresponding changes of signal pathways. The results revealed that treatment with GW9508 could significantly ameliorate cognitive deficits of APP/PS1 mice, upregulate the expression levels of cAMP, p-CREB and neurotrophic factors in vivo, while GW9508 also ameliorate Aβ

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Apoptosis Regulatory Proteins; Benzoates; Cognition Disorders; Cyclic AMP; Cyclic AMP Response Element-Binding Protein; Down-Regulation; Male; Maze Learning; Methylamines; Mice; Neurons; Peptide Fragments; Presenilin-1; Propionates; Pyrimidines; Recognition, Psychology; Signal Transduction