The Role Of GPR50in The Pathogenesis Of Alzheimer’s Disease

Objective:To investigate the function of G protein coupled receptor50(GPR50) in ADpathology in APP/PS1transgenic mice model.Methods:Adeno-associated viruses (AAV) encoding GPR50or EGFP were injected into thehippocampus of APP/PS1mouse by using stereotactic injection at4months old.3~4months after injection, the coronal sections of the cortex and hippocampus of APP/PS1mice were stained for Aβ, GFAP (a maker of astrocytes), Iba-1(a maker of microglia), andsynaptophysin (a maker of synapse). The numbers and the size of Aβ plaques, the densityof GFAP+cells, Iba-1+cells and synaptophysin+signals were quantified and analyzed.Morris water maze analysis was performed to investigate the function of GPR50inlearning and memory of APP/PS1mice.Results:The numbers and the size of Aβ plaques, the volume of GFAP+cells or Iba-1+cells weredecreased, while the immunoreactivity of synaptophysin increased, in the hippocampus ofGPR50-injected compared to that of EGFP-injected APP/PS1mice. GPR50-injected APP/PS1mice exhibited reduced escape latency, fast learning trend and crossed the targets more times inthe probe trial in Morris water maze test. These results indicate that overexpression of GPR50attenuates the deficits of learning and memory in APP/PS1mice.Conclusion:Overexpression of GPR50inhibits the generation of Aβ and the activation ofastrocytes and microglia in APP/PS1mice. Overexpression of GPR50attenuates the lossesof synapses and the deficits of cognition in APP/PS1mice. GPR50plays essential roles inthe pathogenesis of AD.