Effects Of Orientin On Cognitive Function And Autophagy In APP/PS1 Transgenic Mice

ObjectiveTo study the influence of orientin on cognitive function in APP/PS1 double transgenic mice and probable mechanisms.MethodsThe mice(7 months of age)were randomly assigned into three groups(n=8 in each group): non-transgenic mouse(NT)and APP/PS1 transgenic mouse(Tg)were with saline,and APP/PS1 transgenic mouse with orientin(Tg+Ori),and were injected intraperitoneally once per day for 30 day.Morris Water Maze test was carried out for the evaluation of spatial learning and memory.The measurement of A? was conducted by immunohistochemical stain.Autophagy related protein expression of LC3-?,p62,Cathepsin D and beclin-1 were measured by Western Blotting.ResultsCompared with NT group,Tg mice showed deficit in memory formation,enhanced A? deposition and protein level of LC3-?,p62 and Cathepsin D;compared with Tg group,Tg+Ori mice showed improved learning and memory,decreased A? load,and levels of LC3-?,p62 and Cathepsin D were increased.The level of beclin-1 showed no difference between groups.ConclusionsIn this study,our results showed that APP/PS1 transgenic mice exhibit impaired learning and memory,massive deposition of A? in the brain,impaired autophagic substrate degradation and autolysosomal accumulation.Ori treatment enhanced autophagic clearance and decreased the abnormal accumulation of autolysosomes to ameliorate autophagy dysfunction,leading to decreased brain A? deposition and improved learning and memory in APP/PS1 transgenic mice.Therefore,Ori might be a promising candidate agent for the treatment of AD.