Comparative Study On Dynamic Changes Of Cognitive Function And Brain Pathological Characteristics Between Ob/ob Model Mice And APP/PS1 Model Mice

Objective: To examine the changes of Amyloid beta peptide expression and its related metabolic enzymes in the brains of Alzheimer's disease(AD)and ob /ob mice(type 2 diabetes mellitus,T2DM),so as to explore the possible mechanism of type 2 diabetes mellitus combined with AD.Methods:Different ages of male APP/PS1 double transgenic mice,ob/ob mice and the wild-type control mice at the age of 5 mouth,9 mouth,12 mouth were employed in this study(5 for each group).Morris water maze,Immunohistochemical(IHC),Thioflavine S(Th-S),Elisa and Western blot were used to conducted to observe the effect of liquirtigenin on the spatial learning and memory,detect amyloid senile plaques(SP),A?and Alzheimer's disease related metabolic protein.Results:In the Morris water maze test: APP/PS1,ob/ob and control group was no difference in escape latency and path length(P>0.05)in the visible platform;in the hidden platform experiment APP/PS1 and ob/ob group had more latency(P<0.05)and further path length(P<0.05);In the probe test,platform-passing times in the APP/PS1 and ob/ob group were significantly lesser than control group(P<0.05).IHC and Th-S staining showed that a certain number of SPs were observed in the cerebral cortex and hippocampus of APP/PS1 mice;SPs were occasionally observed in the cortex of ob/ob mice,while no SP appeared in wild-type mice.ELISA assay showed that A?40 and A?42levels were significantly increased in APP/PS1 and ob/ob mice brains as compared with controls(P<0.05),thought both A?40 and A?42 levels in AD mice were significantly higher than those of ob/ob mice(P<0.05).The Western blot analysis showed that amyloid precursor protein(APP)expression level was highest in APP/PS1 mice among 3 groups,and its expressed higher in ob/ob mice than that of control mice(P<0.05).BACE1 expression was notably increased in APP/PS1 and ob/ob mice as compared with control(P<0.05),however,it expressed higher in APP/PS1 mice than ob/ob mice(P<0.05).The expression of A? degradation enzyme IDE ?NEP was reduced in APP/PS1 and ob/ob mice(P<0.05),while lowest in ob/ob mice.Conclusion:There were similar SPs in T2DM model mice,and the pathological changes of dementia were observed in the brain of T2DM model mice.The ability of spatial learning and memory in T2DM model mice may be related to the pathogenesis of dementia.Abnormal production,degradation and gathering of A? are not only occurred in the early stage of AD,but also in the brain of T2DM.These results indicate that overexpression of A? may be one of main reasons for T2DM combined AD.