Coenzyme Q10 and exercise training reinstate middle cerebral artery occlusion-induced behavioral deficits and hippocampal long-term potentiation suppression in aging rats.

RATIONAL: Patients experience post-stroke cognitive impairment during aging. To date, no specific treatment solution has been reported for this disorder. OBJECTIVE: The purpose of this study was to evaluate the effects of exercise training and coenzyme Q10 supplementation on middle cerebral artery occlusion (MCAO) induced behavioral impairment, long-term potentiation inhibition and cerebral infarction size in aging rats. METHODS: Fifty aging male rats underwent MCAO surgery and were randomly distributed in to the following groups: 1-Sham, 2- control, 3- Coenzyme Q10, 4- Exercise training and 5- Exercise training with Q10 supplementation (Ex + Q10). Aerobic training groups were allowed to run on a treadmill for 12 weeks. Q10 (50 mg/kg) was administered intragastrically by gavage. Morris water maze, shuttle box and elevated plus maze tests were used to evaluate cognitive function. The population spike (PS) amplitude and slope of excitatory postsynaptic potentials (EPSP) in the dentate gyrus area were recorded as a result of perforant pathway electrical stimulation. RESULTS: Our study showed that Q10 and aerobic training alone ameliorate spatial memory in the acquisition phase, but have no effect on spatial memory in the retention phase. Q10 and exercise training synergistically promoted spatial memory in the retention phase. Q10 and exercise training separately and simultaneously mitigated cerebral ischemia-induced passive avoidance memory impairment in acquisition and retention phases. The EPSP did not differ between the groups, but exercise training and Q10 ameliorate the PS amplitude in hippocampal responses to perforant path stimulation. Exercising and Q10 simultaneously reduced the cerebral infarction volume. CONCLUSION: Collectively, the findings of the present study imply that 12 weeks of aerobic training and Q10 supplementation alone can simultaneously reverse cerebral ischemia induced neurobehavioral deficits via amelioration of synaptic plasticity and a reduction in cerebral infarction volume in senescent rats.

Comparison of the preconditioning effect of different exercise training modalities on myocardial ischemia-reperfusion injury.

The study of exercise preconditioning can develop strategies to prevent cardiovascular diseases and outline the efficient exercise model. However, the exercise type with the most protective effect against ischemia-reperfusion injury is unknown. In this study, we examined the effects of three kinds of exercise preconditioning on myocardial ischemia-reperfusion in adult rats and explored the possible underlying mechanisms. Male Wistar rats subjected to ten weeks of endurance, resistance, and concurrent training underwent ischemia (30 min) and reperfusion (120 min) induction. Then, infarction size, serum levels of the CK-MB, the redox status, and angiogenesis proteins (VEGF, ANGP-1, and ANGP-2) were measured in the cardiac tissue. Results showed that different exercise training modes have the same reduction effects on infarction size, but ischemia-reperfusion-induced CK-MB was lower in response to endurance training and concurrent training. Furthermore, cardiac VEGF levels increased in all three kinds of exercise preconditioning but ischemia-reperfusion-induced ANGP-1 elevated more in endurance training. The cardiac GPX activity was improved significantly through the resistance and concurrent exercise compared to the endurance exercise. In addition, all three exercise preconditioning models decreased MPO levels, and ischemia reperfusion-induced MDA was lower in endurance and resistance training. Overall, these results indicated that cardioprotection of exercise training against ischemia-reperfusion injury depends on the exercise modality. Cardioprotective effects of aerobic, resistance, and concurrent exercises are due to different mechanisms. The preconditioning effects of endurance training are mediated mainly by pervasive angiogenic responses and resistance training through oxidative stress amelioration. The preconditioning effects of concurrent training rely on both angiogenesis and oxidative stress amelioration.

The preconditioning effect of different exercise training modes on middle cerebral artery occlusion induced-behavioral deficit in senescent rats.

Introduction: Brain abilities decrease after brain stroke in elderly. The neuroprotective effect of exercise training has been proved in clinical trials and animal experiment. Nevertheless, it is not still clear what kind of exercise has greater protective effect. The present study aimed at investigating pre-conditioning effect of endurance, resistance, and concurrent training on learning ability, anxiety, and spatial memory in aged rats following stroke strength with middle cerebral artery occlusion. Method: We used 50 male Wistar rats (age = 24 months) that were assigned randomly in five groups; 1: sham group, 2: Control group 3: Endurance training 4: Resistance training, and 5: concurrent training. The exercise training groups received training for four weeks. Following training, middle cerebral artery occlusion was applied to induce cerebral ischemia. Using the elevated plus maze, shuttle box test, and Morris water maze, neurocognitive functions were tested in the sample rats. Results: It was found that resistance training did not affect spatial memory in the acquisition phase, while concurrent training and endurance training enhanced spatial memory in the acquisition phase. On the contrary, spatial memory was improved by resistance training in the retention phase, while concurrent and endurance exercises did not affect spatial memory in the retention phase. Passive avoidance learning ability at acquisition phase was more in resistance group compared to the endurance and concurrent training in shuttle box test, but in retention phase was similar between training groups. Unlike endurance and concurrent training, resistance training reduced anxiety in senescent rats. Conclusion: All three exercise types alleviated aversive learning and memory impairment induced by stroke in senescent rats. Notably, the resistance training showed a greater protective effect compared to the other two training methods.

Interval training and Crataegus persica ameliorate diabetic nephropathy via miR-126/Nrf-2 mediated inhibition of stress oxidative in rats with diabetes after myocardial ischemia-reperfusion injury.

Myocardial disorders are the most common cause of renal failure and mortality in diabetic patients, but the molecular mechanism of this process is not yet clear. The reduction of nuclear Erythroid2-related factor-2 (Nrf-2) and positive regulators of Nrf-2 proteins, such as DJ-1 and microRNA-126 (miR-126), after hypoxia and the promotion of reactive oxygen species, might be an intervention indicator in renal failure after myocardial ischemia-reperfusion. Therefore, this study evaluates the renoprotective effect of exercise training and Crataegus persica extract (CE) on myocardial ischemia-reperfusion-induced kidney injury in diabetic rats. Fifty rats were divided into five groups: healthy sedentary control (Con), sedentary diabetic (D), interval trained diabetic (TD), diabetic plus Crataegus persica extract treatment (CD), and interval trained diabetic plus Crataegus persica extract treatment (TCD) groups. The rats in the exercise groups were subjected to moderate-intensity interval training five days per week for ten weeks. The rats in CD and TCD groups received 300 mg/kg of Crataegus persica through gavage for ten weeks. Then, the subjects underwent 30 min of myocardial ischemia and subsequently reperfusion for 24 h. At the end of the experiment, insulin sensitivity, oxidative stress, renal function, histopathology of the kidney, Nrf-2, miR-126, and DJ-1 gene expression levels were evaluated. The results show that the treatments decreased elevated levels of renal oxidative stress, glomerular filtration rate, insulin sensitivity, and pathological score in diabetic rats. Also, the expression of Nrf-2 and miR-126, unlike DJ-1, decreased in diabetic rats due to interval training. Due to the results, diabetes aggravates acute myocardial ischemia-reperfusion-induced kidney injury, while moderate-intensity interval training and Crataegus persica treatment simultaneously ameliorate myocardial ischemia-reperfusion-induced renal injury via miR-126/Nrf-2 pathway and improve insulin sensitivity and renal function in type 1 diabetic rats.

Cardioprotective effects of exercise preconditioning on ischemia-reperfusion injury and ventricular ectopy in young and senescent rats.

BACKGROUND: Aging decreases ischemic tolerance, while exercise prevents myocardial ischemia reperfusion (IR) injury. The cardioprotective role of high intensity interval training (HIIT), however, is unknown. METHODS: Accordingly, we investigated 8 weeks (5 days/week, 40 min/day) of HIIT treadmill exercise (60%/90% of VO2 peak) on IR injury in young (2-month) and senescent (20-month) Wistar rat myocardia (N = 10/group). Surgical IR (30 min/120 min) was performed via reversible left anterior descending artery ligation and ECG was analyzed to determine ventricular ectopy during IR period. RESULTS: Infarction size and oxidative stress were measured in hearts post-mortem. Glutathione peroxidase activity and Myeloperoxidase levels were mitigated with age, but elevated post IR. HIIT potentiated antioxidant defenses in young and old hearts, and infarction size was lower in young HIIT trained. Metrics of reactive oxygen species were not lower after IR, and were not affected by HIIT in young or old rats. Ventricular ectopy score in senescent rats was insignificantly more than young rats and HIIT significantly decreased ventricular ectopy score in young and senescent rats. CONCLUSIONS: Findings indicate that IR tolerance is mitigated in senescent hearts, while HIIT ameliorated infarction by increasing antioxidant enzymes activity in young and senescent hearts.

The effect of different exercise training modes on dentate gyrus neurodegeneration and synaptic plasticity in morphine-dependent rats.

Various impacts of exercise on brain performance following the induction of morphine dependence have been documented; however, the underlying neuronal mechanisms are still unclear. The present research was done to investigate the impact of different exercise training modes on apoptosis, neuronal maturation, and synaptic plasticity in the perforant pathway (PP)-dentate gyrus (DG) synapses in the morphine-dependent rats. Five groups, including a control group (Con, ten healthy rats) and forty morphine-dependent rats were considered as follows (n = 10/group): 1) sedentary-dependent (Sed-D); 2) endurance exercise-dependent (En-D); 3) strength exercise-dependent (St-D); and 4) concurrent exercise-dependent (Co-D). The exercise training groups were subjected to endurance, strength, and concurrent training five days a week for ten weeks. After training sessions, the field excitatory postsynaptic potential (fEPSP) slope and population spike (PS) amplitude in the DG were determined in response to high-frequency stimulation (HFS) of the PP. For assessing neurogenesis and apoptosis, NeuroD and Caspase-3 expression levels were evaluated after all experiments. Concurrent training increased PS amplitude and EPSP compared to the control group. NeuroD in the morphine-dependent rats significantly decreased, but concurrent training returned the NeuroD to its levels in healthy rats. Furthermore, Caspase-3 expression levels in morphine-dependent rats remarkably increased and concurrent training significantly reduced Caspase-3 expression levels compared to the Sed-D group. Concurrent training can ameliorate synaptic plasticity impairment in morphine-dependent rats through neurogenesis promotion and apoptosis reduction. According to the results, concurrent training can be an appropriate novel candidate for treating opioid addiction.

Cardioprotective effect of resistance training and Crataegus oxyacantha extract on ischemia reperfusion-induced oxidative stress in diabetic rats.

Discovering an effective approach to limit infarction size after ischemia-reperfusion has a clinical importance in diabetics. We investigated the anti-myocardial ischemia-reperfusion injury effect of resistance training and Crataegus oxyacantha extract on diabetic rats. To this end, 50 male Wistar rats were randomly divided into 5 groups: the sedentary control (SC), sedentary diabetic (SD), resistance trained diabetic (RD), diabetic plus C. oxyacantha extract treatment (CD) and resistance trained diabetic plus C. oxyacantha extract treatment (RCD) groups. Animals in trained groups were subjected to progressive resistance training program with the use of a ladder (5 days/week, for 10 weeks). C. oxyacantha extract rats were treated with 100 mg/kg body weight of the extract using a gavage every day for 10 weeks. After treatments, rats were subjected to ischemia via LAD artery ligation for 30 min followed by 90 min reperfusion. The heart was collected following the ischemia-reperfusion and analyzed for oxidative stress and ischemia-reperfusion injury. Compared to the SC group, LDH, CK-MB and infarction size in the SD group were significantly higher, whereas injury indices in the RCD group were significantly lower than those in the SD group. GPx and MPO levels after reperfusion increased and decreased, respectively in response to training and C. oxyacantha. These findings suggest that 10 weeks resistance training and C. oxyacantha can synergistically decrease ischemia-reperfusion injury, and this mechanism may be related to a reduction in oxidative stress which is normally associated with ischemia-reperfusion.

Resistance training and hawthorn extract ameliorate cognitive deficits in streptozotocin-induced diabetic rats.

It has been shown that diabetic rats display cognitive impairment. The aim of this study was to investigate the effects of resistance training and natural antioxidants on learning and memory in type 1 diabetic rats. For this purpose, fifty male Wistar rats were randomly divided into five groups: (i) Control (Con, n=10), (ii) Diabetic (D, n=10), (iii) Diabetic+Resistance training (DRT, n=10), (iv) Diabetic+natural antioxidants (DHE, n=10), and (v) Diabetic+Resistance training+ natural antioxidants (DRH, n=10). Climbing the ladder for a period of 5days/week for 10 consecutive weeks was considered as the resistance training model in our study. Natural antioxidants (100mg/kg per day) were administered to natural antioxidant groups for a period of 10 weeks. Moreover, spatial and passive avoidance learning and memory function were evaluated by Morris Water Maze (MWM) and shuttle box tests. The results showed that, mean of total escape latency decreased 25% (P<0.0001) in the DRH group compared with the D group in MWM. The percentage of time spent in the target quadrant identically decreased (34%) in the D and DHE groups compared with the Con group (p=0.001). In this regard, time spent in the dark Compartment (TDC) respectively rose 86% and 95% in the D and DHE groups compared with the Con group (p<0.05), and decreased 88% in the DRT and DRH groups compared with the D group in the shuttle box test (p<0.05). Furthermore, we noticed that total antioxidant capacity increase and lipid peroxidation decrease in response to the treatments in the diabetic rats as well. Therefore, the current study indicated that exercise training and natural antioxidants synergistically ameliorated learning and memory deficits in type 1 diabetic rats via reducing oxidative stress. Hence, it may propose a potential role of resistance training and natural antioxidants as an adjuvant therapy for the prevention and treatment of diabetic complications.

Effects of endurance, resistance, and concurrent exercise on learning and memory after morphine withdrawal in rats.

AIMS: Continuous morphine consumption contributes to the development of cognitive disorders. This work investigates the impacts of different types of exercise on learning and memory in morphine-dependent rats. MAIN METHODS: Forty morphine-dependent rats were randomly divided into five groups: sedentary-dependent (Sed-D), endurance exercise-dependent (En-D), strength exercise-dependent (St-D), and combined (concurrent) exercise-dependent (Co-D). Healthy rats were used as controls (Con). After 10weeks of regular exercise (endurance, strength, and concurrent; each five days per week), spatial and aversive learning and memory were assessed using the Morris water maze and shuttle box tests. KEY FINDINGS: The results showed that morphine addiction contributes to deficits in spatial learning and memory. Furthermore, each form of exercise training restored spatial learning and memory performance in morphine-dependent rats to levels similar to those of healthy controls. Aversive learning and memory during the acquisition phase were not affected by morphine addiction or exercise, but were significantly decreased by morphine dependence. Only concurrent training returned the time spent in the dark compartment in the shuttle box test to control levels. SIGNIFICANCE: These findings show that different types of exercise exert similar effects on spatial learning and memory, but show distinct effects on aversive learning and memory. Further, morphine dependence-induced deficits in cognitive function were blocked by exercise. Therefore, different exercise regimens may represent practical treatment methods for cognitive and behavioral impairments associated with morphine-related disease.