Alzheimer's disease complicated with type 2 diabetes and hippocampal injury: from oxidative stress to autophagy / 中华神经科杂志

ABSTRACT

Objective To study the pathological alterations,such as oxidative stress,cell proliferation and insulin resistance,especially autophagy,in Alzheimer' s disease (AD) complicated with type 2 diabetes (AD + T2DM).Methods The mouse models of T2DM,AD and AD + T2DM were used in the study,and totally 80 mice were divided into four groupscontrol group,T2DM group,AD group and AD + T2DM group.Morris water maze was applied to test the ability of learning and memory among the above mentioned groups.In the meantime,insulin resistance index,the expression of insulin receptor substrate 2,oxidative stress,cell proliferation and autophagy were observed with chemical analysis,immunofluorescent labeling,transmission electron microscopy and Western blotting.Results On day 4,the difference of time to find Morris water maze in control group,T2DM group,AD group and AD + T2DM group ((26.08 ±4.93) s,(38.46 ± 4.07) s,(47.32 ± 5.86) s,(53.01 ± 6.12) s,F =2.454,P =0.025) was statistically significant,and the time in AD + T2DM group was longer than that in AD group (t =-3.624,P =0.033).Compared with control group,insulin resistance occurred in T2DM group,AD group and AD + T2DM group (4.35 ± 0.48,16.12 ± 3.57,7.03 ± 3.11,18.78 ± 5.06,F =5.602,P =0.009),and the reduction of insulin receptor substrate 2 expression,the oxidative stress reaction,neural proliferative suppression and autophagy (F =418.344,222.514,436.250,113.934,23.772,35.469,all P ＜ 0.05) were induced in T2DM group,AD group and AD + T2DM group,which were more serious in AD + T2DM group than in AD group (t =-2.796,21.723,-8.041,9.037,-4.403,-32.011,-26.593,all P ＜0.05).Conclusion AD + T2DM mice suffered more serious cognitive impairment than AD and T2DM mice.The oxidative stress levels of AD + T2DM mice were upregulated,and thus led to the inhibition of cell proliferation,eventually leading to promotion of autophagy.