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Evidence-Based Complementary and Alternative Medicine
Volume 2018, Article ID 2901863, 9 pages
Research Article

Chronic Unpredictable Mild Stress Aggravates Mood Disorder, Cognitive Impairment, and Brain Insulin Resistance in Diabetic Rat

1Pharmacology Research Center, First Affiliated Hospital, Hunan University of Chinese Medicine, Changsha, Hunan, China
2The Domestic First Class Construction Discipline of Chinese Medicine in Hunan University of Chinese Medicine, Changsha, Hunan, China
3Key Laboratory of Chinese Material Medical Power and Innovation Drugs Established by Provincial and Ministry, Hunan University of Chinese Medicine, Changsha, Hunan, China
4Institute of Innovation and Applied Research, Hunan University of Chinese Medicine, Changsha, Hunan, China

Correspondence should be addressed to Yuhong Wang; moc.361@701_hyw

Received 13 August 2018; Revised 29 September 2018; Accepted 21 November 2018; Published 3 December 2018

Academic Editor: Vincenzo De Feo

Copyright © 2018 Hui Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.