Abstract
Diabetes-induced brain insulin resistance is associated with many mental diseases, including depression. Epidemiological evidences demonstrate the pathophysiologic link between stress, depression, and diabetes. This study was designed to determine whether chronic unpredictable mild stress- (CUMS-) induced changes in brain insulin resistance could contribute to deterioration in mood and cognitive functions in diabetic rats. Male SD rats were randomly assigned to three groups, including standard control group, the diabetes group, and the diabetes with CUMS group. After 7 weeks, emotional behaviors and memory performances as well as metabolic phenotypes were measured. In addition, we examined the changes in protein expression related to brain insulin signaling. Our results show that rats in diabetes with CUMS group displayed a decreased locomotor behavior in open-field test, an increased immobility time in forced swim test, and tail suspension test, and an impaired learning and memory in the Morris water maze when compared to animals in diabetes group. Further, diabetes with CUMS exhibited a significant decrease in phosphorylation of insulin receptor and an increase phosphorylation of IRS-1 in brain. These results suggest that the depression-like behaviors and cognitive function impairments in diabetic rats with CUMS were related to the changes of brain insulin signaling.
Highlights
More than 382 million patients worldwide suffered from diabetes mellitus in 2013, and this number will reach 592 million in 2035 [1]
Diabetes usually causes a number of complications involving brain function which related to cognitive decline and depression [22]
Can et al found that diabetes mellitus (DM) causes depression deterioration, and spontaneous locomotor activities were decreased accompanied with learning parameters impairment [9]
Summary
More than 382 million patients worldwide suffered from diabetes mellitus in 2013, and this number will reach 592 million in 2035 [1]. The prevalence of depression in people with diabetes may run up to 38.75%. Among these people, 48.38% were found suffering from moderately depressed [2]. A cross-sectional study [3] described that 35.1% patients with diabetes were diagnosed depression symptoms. The government did not pay attention to the increase prevalence of depression and diabetes and its health services. The researches associated with pathophysiological mechanisms of depression in patients with diabetes were insufficient. The association between depression and insulin resistance (IR) can explain the biological link between depression and type 2 diabetes [7]. Understanding the disordered systemic IR and defective brain insulin signaling in comorbidity of diabetes and depression has become a topic of concern and public health challenge
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