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

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.

Download Full-text

Skeletal Muscle Metabolomic Responses to Endurance and Resistance Training in Rats under Chronic Unpredictable Mild Stress

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18041645 ◽

2021 ◽

Vol 18 (4) ◽

pp. 1645

Author(s):

Xiangyu Liu ◽

Xiong Xue ◽

Junsheng Tian ◽

Xuemei Qin ◽

Shi Zhou ◽

...

Keyword(s):

Resistance Exercise ◽

Endurance Exercise ◽

Field Tests ◽

Treadmill Running ◽

Control Group ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress ◽

Sprague Dawley ◽

Exercise Interventions ◽

Sprague Dawley Rats

The objectives of this study were to compare the antidepressant effects between endurance and resistance exercise for optimizing interventions and examine the metabolomic changes in different types of skeletal muscles in response to the exercise, using a rat model of chronic unpredictable mild stress (CUMS)-induced depression. There were 32 male Sprague-Dawley rats randomly divided into a control group (C) and 3 experimental groups: CUMS control (D), endurance exercise (E), and resistance exercise (R). Group E underwent 30 min treadmill running, and group R performed 8 rounds of ladder climbing, 5 sessions per week for 4 weeks. Body weight, sucrose preference, and open field tests were performed pre and post the intervention period for changes in depressant symptoms, and the gastrocnemius and soleus muscles were sampled after the intervention for metabolomic analysis using the 1H-NMR technique. The results showed that both types of exercise effectively improved the depression-like symptoms, and the endurance exercise appeared to have a better effect. The levels of 10 metabolites from the gastrocnemius and 13 metabolites from the soleus of group D were found to be significantly different from that of group C, and both types of exercise had a callback effect on these metabolites, indicating that a number of metabolic pathways were involved in the depression and responded to the exercise interventions.

Download Full-text

γ-PGA-Rich Chungkookjang, Short-Term Fermented Soybeans: Prevents Memory Impairment by Modulating Brain Insulin Sensitivity, Neuro-Inflammation, and the Gut–Microbiome–Brain Axis

Foods ◽

10.3390/foods10020221 ◽

2021 ◽

Vol 10 (2) ◽

pp. 221

Author(s):

Do-Youn Jeong ◽

Myeong Seon Ryu ◽

Hee-Jong Yang ◽

Sunmin Park

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Gut Microbiome ◽

Memory Impairment ◽

Memory Function ◽

Bacillus Species ◽

Fermented Foods ◽

Short Term ◽

Brain Insulin ◽

Brain Insulin Resistance

Fermented soybean paste is an indigenous food for use in cooking in East and Southeast Asia. Korea developed and used its traditional fermented foods two thousand years ago. Chungkookjang has unique characteristics such as short-term fermentation (24–72 h) without salt, and fermentation mostly with Bacilli. Traditionally fermented chungkookjang (TFC) is whole cooked soybeans that are fermented predominantly by Bacillus species. However, Bacillus species are different in the environment according to the regions and seasons due to the specific bacteria. Bacillus species differently contribute to the bioactive components of chungkookjang, resulting in different functionalities. In this review, we evaluated the production process of poly-γ-glutamic acid (γ-PGA)-rich chungkookjang fermented with specific Bacillus species and their effects on memory function through the modulation of brain insulin resistance, neuroinflammation, and the gut–microbiome–brain axis. Bacillus species were isolated from the TFC made in Sunchang, Korea, and they included Bacillus (B.) subtilis, B. licheniformis, and B. amyloliquefaciens. Chungkookjang contains isoflavone aglycans, peptides, dietary fiber, γ-PGA, and Bacillus species. Chungkookjangs made with B. licheniformis and B. amyloliquefaciens have higher contents of γ-PGA, and they are more effective for improving glucose metabolism and memory function. Chungkookjang has better efficacy for reducing inflammation and oxidative stress than other fermented soy foods. Insulin sensitivity is improved, not only in systemic organs such as the liver and adipose tissues, but also in the brain. Chungkookjang intake prevents and alleviates memory impairment induced by Alzheimer’s disease and cerebral ischemia. This review suggests that the intake of chungkookjang (20–30 g/day) rich in γ-PGA acts as a synbiotic in humans and promotes memory function by suppressing brain insulin resistance and neuroinflammation and by modulating the gut–microbiome–brain axis.

Download Full-text

GR/NF-κB signaling pathway regulates hippocampal inflammatory responses in diabetic rats with chronic unpredictable mild stress

European Journal of Pharmacology ◽

10.1016/j.ejphar.2021.173861 ◽

2021 ◽

Vol 895 ◽

pp. 173861

Author(s):

Zi-Rong Li ◽

Yuan-Shan Han ◽

Zhuo Liu ◽

Hong-Qing Zhao ◽

Jian Liu ◽

...

Keyword(s):

Signaling Pathway ◽

Inflammatory Responses ◽

Diabetic Rats ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress

Download Full-text

Berberine and Ginsenoside Rb1 Ameliorate Depression-Like Behavior in Diabetic Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x21500579 ◽

2021 ◽

pp. 1-19

Author(s):

Jing-Hua Zhang ◽

Hui-Zeng Yang ◽

Hao Su ◽

Jun Song ◽

Yu Bai ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Metabolism ◽

Plasma Cortisol ◽

Adrenocorticotropic Hormone ◽

Morphological Changes ◽

Diabetic Rats ◽

Diabetic Patients ◽

Mild Stress ◽

Ginsenoside Rb1 ◽

Nissl Staining

Rhizoma coptidis(Huang-lian) and Asian ginseng have been widely used in the treatment of diabetes and other concurrent diseases with apparent effects. This study investigated the effects of the active ingredients of R. coptidis and ginseng, berberine and ginsenoside Rb1, on depression-like behavior in a rat diabetes model. The animal model was established via a high-fat diet and intraperitoneal injection of streptozotocin, while the animal’s depression-like behavior was induced via chronic unpredictable mild stress. These experimental rats were divided into four groups: control, depression-like behavior (DLB), metformin plus fluoxetine hydrochloride (M+FH), and berberine plus ginsenoside Rb1 (B+GRb1) groups. Glucose metabolism and insulin resistance were evaluated by oral glucose test and glucose clamp study. Depression-like behavior was evaluated via behavioral analyses, including forced swim, sucrose preference, elevated plus maze, and open-field tests. HE and Nissl staining, plasma cortisol expression of adrenocorticotropic hormone, and brain-derived neurotrophic factor (BDNF) levels were assayed to explore the mechanisms of action. Compared with the control, rats in the DLB group had a significant increase in the levels of blood glucose and depression-like behavior. The B+GRb1 group significantly improved glucose metabolism and insulin resistance, reduced depression-like behavior, downregulated levels of plasma cortisol and adrenocorticotropic hormone under stress, and upregulated BDNF protein expression compared to the DLB rats. HE and Nissl staining data revealed that B+GRb1 protected neurons from pathological and morphological changes. Thus, berberine and ginsenoside Rb1 not only improved glucose metabolism in diabetic rats but also ameliorated their depression-like behavior under chronic unpredictable stress. Mechanistically, studied data with plasma hormonal levels and brain neuronal pathological/morphological changes supported the observed effects. The combination of berberine and ginsenoside Rb1 may have a clinical value in the management of diabetic patients with depression.

Download Full-text