Pouran Karimi

Aims/Introduction Defective insulin signaling in the brain may disrupt hippocampal neuroplasticity resulting in learning and memory impairments. Thus, this study investigated the effect of aerobic exercise training on cognitive function and synaptic protein markers in diabetic rats. Materials and methods Twenty male Wistar rats (200–250 g), were fed on high-fat diet and received a low dose of streptozotocin (35 mg/kg, i.p) to induce type 2 diabetes. Then diabetic animals were randomly divided into sedentary and training groups. The exercise training program was treadmill running at 27 m/min for 60 min/day for 8 weeks. One day after the last training session, Morris Water Maze (MWM) task was performed to evaluate spatial learning and memory. Then, the hippocamp and prefrontal cortex tissues were instantly dissected for immunoblotting assay of BDNF, GSK-3β, p-GSK-3β, P38, p-P38, ERK1/2, p-ERK1/2, heat shock protein-27 (HSP27), SNAP-25, synaptophysin, and PSD-95. Independent t-test analysis and two-way ANOVA was used to determine the differences under significance level of 0.05 using the 26th version of IBM SPSS statistical software. Results The results showed that aerobic exercise improved memory as assessed in the MWM task. Moreover, aerobic exercise up-regulated HSP27 and BDNF protein levels in the prefrontal cortex, and hippocampus coincided with robust elevations in SNAP25 and PSD-95 levels. Moreover, exercise reduced phosphorylated P38, while increased p-ERK1/2 and p-GSK-3β (p). Conclusion Our findings suggest that aerobic exercise may debilitate the harmful effects of diabetes on the cognitive function possibly through enhancing synaptic protein markers.

Diabetic cardiomyopathy (DC) is associated with impaired endoplasmic reticulum (ER) function, development of ER stress, and induction of cardiac cell apoptosis. Preventive effects of BiP inducer X (BIX) were investigated against DC characteristic changes in a type 2 diabetes rat model. To establish diabetes, a high-fat diet and a single dose of streptozotocin were administered. Then, animals were assigned into the following groups: control, BIX, diabetic animals monitored for one, two, and three weeks. Diabetic rats were treated with BIX for one, two, and three weeks. Expressions of various ER stress and apoptotic markers were assessed by immunoblotting method. CHOP gene expression was assessed by Real-time PCR. Tissue expression of BiP was evaluated by immunohistochemistry method. Hematoxylin and eosin and Masson's trichrome staining were performed to assess histological changes in the left ventricle. Cardiac cell apoptosis was examined using TUNEL assay. BIX administration suppressed the activation of the ER stress markers and cleavage of procaspase-3 in the diabetic rats. Likewise, tissue expression of BiP protein was increased, while CHOP mRNA levels were decreased. These results were accompanied by reducing cardiac fibrosis and myocardial cell apoptosis suggesting protective effects of BIX against the development of DC by decreasing cardiomyocyte apoptosis and fibrosis.

Background: According to the experimental studies, the levels of heat shock protein 27 (HSP27) and brain-derived neurotrophic factor (BDNF) are decreased in diabetes which is associated with impaired cognitive function in the brain. Therefore, the increased expression of these two proteins in some brain regions associated with learning and memory can be one of the positive effects of aerobic training on cognition improvement at diabetes. The aim of the present study was to evaluate the effects of aerobic treadmill exercise training (ATET) on HSP27 and BDNF proteins in the prefrontal cortex and hippocampus of streptozotocin (STZ)-induced diabetes in rats. Methods: Twenty healthy adult male Wistar rats approximately 3-month old, weighing 250 ± 25gr were used in this study. Experimental diabetes was induced by a high-fat diet (HFD) for 4 weeks and a low dose of STZ (35 mg/kg, intraperitoneally). Then diabetic animals were divided into two groups (n=10 per each group): control group (C) and aerobic training group (E). The exercise program was treadmill running at 13 m/min, 25 min/day, for 5 days/week at 0˚ slope for the first week, with a gradual increase to 27 m/min for 60 min/day in week 8. Un-paired t-test was used to compare two groups with the considered significant at p<0.05. Results: The results showed that ATET significantly increased protein expression of HSP27 and BDNF in the hippocampus and prefrontal cortex as compared to C group. Conclusion: Our findings showed that aerobic treadmill exercise program can increase the protein expression of HSP27 and BDNF associated with cognition and synaptic plas­ticity and thus counteract the neurodegenerative diseases of the nervous system.

Background: Apoptosis is the physiological cell death that in natural conditions leads to the elimination of old, damaged, waste, and harmful cells. The aim of this study was the effect of eight weeks of high-intensity interval training (HIIT) with and without caloric restriction on gene expression of myocardial Bax and Bcl2 in mice. Methods: Present study was an experimental multi-group design with a control group conducted on 30 two-month old male mice. Subjects were divided into five homogenous groups including base control, control, caloric restriction, interval exercise training, and caloric restriction + interval exercise training. Training groups participated in interval exercise training five sessions per week for 8 weeks. The level of gene expression of myocardial Bax and Bcl2 was evaluated by real-time PCR. Data were analyzed using the one-way ANOVA at the level of (P<0.05). Results: The results showed that the training group had a significant increase in gene expression of myocardial Bcl2 in comparison with caloric restriction + exercise training (P<0.05) and a significant decrease in gene expression of myocardial Bax compared to the caloric restriction group (P<0.05). Also, exercise training and exercise training + caloric restriction significantly increased the gene expression of myocardial Bcl2 and significantly decreased Bax/Bcl2 ratio compared to caloric restriction, base control, and control (P< 0.05). Conclusion: It seems that high-intensity interval training without caloric restriction would provide a suitable environment for increasing the integrity of the mitochondrial membrane of myocardial cells and possibly apoptosis.

Objective: Some previous studies have shown the protective effect of caffeine on apoptosis through the regulation of pro- and anti-apoptotic proteins. The aim of this study was to investigate the effects of chronic caffeine administration on the expression ratio of B-cell lymphoma protein 2 (Bcl-2) and Bcl-2-Associated X-protein (Bax) proteins in the cardiac tissue of rats with Type 2 Diabetes. Methods: In this experimental study, samples were 24 male white wistar rats (aged 2-3 months with a weight of 250-300 g) randomly divided into three groups: Healthy control (n=8), untreated diabetic (n=8), and diabetic with caffeine supplement (n=8; 70 mg/kg-1 for 8 weeks, 5 days a week). The expression of proteins associated with apoptotic signaling pathway (Bax and Bcl-2) in the cardiac muscle (left ventricular) was measured by Western blot method. One-Way Variance (ANOVA), t-test, and Tukey’s post hoc test were used for data analysis. Results: Induction of type two diabetes significantly increased the expression of Bax protein (1.81±0.2) and decreased the expression of Bcl-2 protein (0.36±0.05) compared to control group (P=0.001). However, caffeine administration increased the expression of Bax protein (131%) compared to diabetic control group (P=0.001). Therefore, caffeine administration after diabetes induction elevated the Bax/Bcl-2 ratio (P=0.001). Conclusion: Eight weeks of caffeine administration have an exacerbating effect on the apoptotic cell death caused by type 2 diabetes by increasing pro-apoptotic proteins and reducing anti-apoptotic proteins.

Background and Aim Apoptosis or programmed death is active biological process and reversible that the balance between growth and cell death in various tissues, particularly myocardial tissue is essential role. The aim of this study was the effect of 8 weeks High Intensity Interval Training (HIIT) with and without food restriction on gene expression of Caspase 3 and 9 in rats. Methods & Materials: This study was experimental multi group design with control group which conducted on 30 rats with two months old male. Subjects were divided in to five homogenous groups including base control, control, caloric restriction, interval exercise training and caloric restriction+interval exercise training. Training groups five sessions in weeks were participated in interval exercise training for 8 weeks. The level of gene expression of the proteins Caspase 3 and 9 was evaluated by Real Time-PCR. Dates were analyzed using the 1-way ANOVA at the level of (P<0.05). Ethical Considerations: The protocol of this study was approved by the Medical Committee of Sanandaj University of Medical Sciences (Code: IR.MYK.REC.1397.5022). Results: The results showed that the training group had a significant decrease in gene expression of Caspase 3 in comparison with caloric restriction+exercise training (P<0.05). Also, exercise training and exercise training+caloric restriction significantly decrease in the gene expression of Caspase 9 compared to caloric restriction, base control and control (P<0.05) and significantly decrease in the gene expression of Caspase 3 compared to base control and control (P<0.05). Conclusion: According to the results, it seems that high intensity interval training with and without calorie restriction provides the necessary adaptations to inhibit or stop apoptosis induced by aerobic exercise.

Background: Diabetes affects cognitive function, synaptic plasticity, synaptogenesis, and neurogenesis in the brain. The exercise improves cognitive function and prevents deleterious alterations in signaling pathways associated with diabetes. The aim of the present study was to evaluate the effects of aerobic treadmill exercise training (ATET) on synaptic proteins in the prefrontal cortex and hippocampus of streptozotocin (STZ)-induced diabetes in rats. Methods: Twenty healthy adult male Wistar rats approximately 3-month old, weighing 250 ± 25gr were used in this study. Experimental diabetes was induced by high-fat diet (HFD) for 4 weeks and a low dose of STZ (35 mg/kg, intraperitoneally). Then diabetic animals were divided into two groups (n=10 per each group): control group (C) and aerobic training group (E). The exercise program was treadmill running at 13 m/min, 25 min/day, for 5 days/week at 0˚ slope for the first week, with a gradual increase to 27 m/min for 60 min/day in the week 8. Results: The ATET significantly increased protein expression of SNAP-25 and PSD-95 in the hippocampus and prefrontal cortex as compared to C group. However, there was no significant difference between synaptophysin levels of the hippocampus and prefrontal cortex in E and C groups. Conclusion: The aerobic treadmill exercise program can attenuate the deleterious effects of diabetes and increased the expression of pre and post-synaptic plas­ticity associated proteins.

This study compares the effect of two types of exercise training, i.e., moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT) on the browning of subcutaneous white adipose tissue (scWAT) in obese male rats. Effects on fat composition, metabolites, and molecular markers of differentiation and energy expenditure were examined. Forty male Wistar rats were assigned to lean (n = 8) or obese (n = 32) groups and fed either a standard chow or high-fat obesogenic diet for 10 weeks. Eight lean and obese rats were then blood and tissue sampled, and the remaining obese animals were randomly allocated into sedentary, MICT, or HIIT (running on a treadmill 5 days/week) groups that were maintained for 12 weeks. Obesity increased plasma glucose and insulin and decreased irisin and FGF-21. In scWAT, this was accompanied with raised protein abundance of markers of adipocyte differentiation, i.e., C/EBP-α, C/EBP-β, and PPAR-γ, whereas brown fat-related genes, i.e., PRDM-16, AMPK/SIRT1/PGC-1α, were reduced as was UCP1 and markers of fatty acid transport, i.e., CD36 and CPT1. Exercise training increased protein expression of brown fat-related markers, i.e., PRDM-16, AMPK/SIRT1/PGC-1α, and UCP1, together with gene expression of fatty acid transport, i.e., CD36 and CPT1, but decreased markers of adipocyte differentiation, i.e., C/EBP-α, C/EBP-β, and plasma glucose. The majority of these adaptations were greater with HIIT compared to MICT. Our findings indicate that prolonged exercise training promotes the browning of white adipocytes, possibly through suppression of adipogenesis together with white to beige trans-differentiation and is dependent on the intensity of exercise.

The balance of pro-angiogenic and anti-angiogenic factors has a significant role in the development of diabetic cardiomyopathy. The purpose of this study was to examine the effect of 8 weeks of high-intensity interval training (HIIT) and moderate intensity continuous training (MICT) on the myocardial angiogenic factors and histological changes in male diabetic rats. Thirty-two male Wistar rats were randomly assigned into four groups: healthy non-exercised control, diabetic (D), D + HIIT, and D+ MICT groups. Diabetes type 2 was induced by a high-fat diet for 2 weeks and a single injection of streptozotocin. Following confirmation of diabetes, animals were subjected to HIIT (90 to 95% of VO2max) or MICT (50–65% of VO2max) protocols 5 days a week for 8 weeks. Western blotting was used for detection of protein expressions of vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), matrix metalloproteinase-2 (MMP2), and tissue inhibitor of matrix metalloproteinase-2 (TIMP2) in the left ventricle. In addition, baseline and final blood glucose and body weight were measured. Histological changes were evaluated using H&E and Masson’s trichrome staining. The results showed that exercise increased protein levels of pro-angiogenic factors while reduced anti-angiogenic factors protein levels in diabetic animals. These changes were followed by increased capillary density and reduced interstitial fibrosis in the left ventricle. Moreover, the MICT was superior to HIIT in enhancing angiogenic factors and attenuation of blood glucose and fibrosis in the diabetic rats. These findings confirm the effectiveness of exercise, particularly MICT, in the improvement of diabetic cardiomyopathy.