Alzheimer’s Disease Companied With Type 2 Diabetes And Hippocampal Injury, From Oxidative Stress To Autophagy

Nowadays, China is becoming an aging country, and the high incidence rate of cardiovascular and cerebrovascular diseases have sounded the alarm for the elderly, among which the Alzheimer’s disease(AD) and Type 2 diabetes(T2DM) are "the two killers" that threaten the health of the elderly, and some scholars consider AD as the "Type 3 diabetes". Another study shows that T2 DM patients have mild cognitive impairment. Moreover, clinical studies have proven that the risk of T2 DM patients suffering from AD is significantly higher than non-diabetics, and there are many AD patients also have T2 DM, which greatly increase the suffering of patients and add more difficulties to the clinical treatment. The human brain has gone through more than 2,500 million years of evolutionary history, and the hippocampus located in the limbic system is responsible for learning and memorizing. When the body encounters adverse external stimuli, the brain’s hippocampus is a more sensitive area, which is why a number of scholars give a detailed study on it. Early in 1962, Ashford and Porter found that there is a phenomenon of "cannibalism(selt-eating)" of cells, which was named by De Duve as "autophagy", which occur in both physiological and pathological processes, so investigating autophagy’s role in various diseases has become a life sciences research focus. This experiment is to study the role of autophagy on Alzheimer’s disease and Type 2 diabetes of hippocampus of mice, and then investigate whether autophagy plays a protective or pathogenic role on this disease.Objective:To study the pathological alterations, such as oxidative stress, cell proliferation and insulin resistance, especially autophagy, in Alzheimer’s disease(AD) companied with type 2 diabetes(AD+T2DM).Methods: The mouse model of type 2 diabetes(T2DM), AD mutant mice were used in the study, and four groups with total 80 cases(control group, T2 DM group, AD group and AD+T2DM group) were divided. Morris water maze was applied to test the ability of learning and memory among various 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 microscope and Western blotting.Results: At day 4, Compared with control group(WT), the learning and memory decreased in T2 DM group, AD group,AD + T2 DM group as well(P<0.05), AD+T2DM is more longer than AD(P<0.05). Insulin resistance occurred in T2 DM group, AD group and AD + T2 DM group as well(P<0.05), with the reduction of insulin receptor substrate 2 expression(P<0.05). On the other hand, the oxidative stress reaction(P<0.05), neural proliferative suppression(P<0.05) and autophagy(P<0.05) were induced in T2 DM, AD groups and the AD + T2 DM group as well. AD+T2DM is more serious than AD(P<0.05).Conclusion: AD + T2 DM mice suffered more serious cognitive impairment than T2 DM and AD mice. The oxidative stress levels of AD + T2 DM mice was upregulated, and thus lead to the inhibition of cell proliferation, Eventually it lead to pomotion of autophagy.