Modulation of mitochondrial phenotypes by endurance exercise contributes to neuroprotection against a MPTP-induced animal model of PD.

AIM: Endurance exercise (EE) has been reported to confer neuroprotection against Parkinson's disease (PD); however, underlying molecular mechanisms of the protection remain still unclear. Since mitochondrial impairment is commonly observed in the brain of PD patients and animals, this study investigated whether EE-induced neuroprotection is associated with mitochondrial phenotypes, using a mouse model of PD induced by intraperitoneal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MAIN METHODS: SH-SY5Y cells were cultured with a neurotoxin MPP+ known to cause PD-like symptoms to examine if modifications of mitochondrial morphology are linked to etiology of PD. For in vivo experiments, C57BL/6 male mice were randomly assigned to four groups: control (CON, n = 12), endurance exercise (EXE, n = 12), MPTP (MPTP, n = 12) and MPTP plus endurance exercise (MPTP + EXE, n = 12). Mice assigned to endurance exercise performed treadmill running at 12 m/min for 60 min/day, 5 days/week for 6 weeks. KEY FINDINGS: SH-SY5Y cells exposed to a neurotoxin MPP+ exhibited mitochondrial fragmentation and diminished mitochondrial proteins, and cell death. Similarly, animals administered with MPTP displayed comparable impairments in the substantia nigra pars compacta (SNpc). In contrast, EE intervention restored motor function to control levels and reduced apoptosis. These propitious effects of EE were associated with mitochondrial phenotypic changes such as upregulated anti-apoptotic proteins (e.g., MCL-1 and BLC-2), reduced a pro-apoptotic protein (e.g., AIF), and improved mitochondrial biogenesis and fusion. SIGNIFICANCE: Our finding that EE-induced mitochondrial phenotypic changes that resist mitochondrial impairment and cell death against PD introduce potential insight into mitochondria as a new therapeutic target for PD.

Endurance Exercise Mediates Neuroprotection Against MPTP-mediated Parkinson's Disease via Enhanced Neurogenesis, Antioxidant Capacity, and Autophagy.

Parkinson's disease (PD) is a neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra, leading to motor dysfunction. Growing evidence has demonstrated that endurance exercise (EE) confers neuroprotection against PD. However, the exact molecular mechanisms responsible for exercise-induced protection of dopaminergic neurons in PD remain unclear. Since oxidative stress plays a key role in the degenerative process of PD. We investigated whether EE-induced neuroprotection is associated with enhanced antioxidative capacity and autophagy, using a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. C57BL/6 male mice were randomly assigned to four groups: control (CON, n = 12), exercise (EXE, n = 12), MPTP (MPTP, n = 12) and MPTP + exercise (MPTP + EXE, n = 12). Our data demonstrated that while MPTP treatment impaired motor function, EE restored MPTP-induced motor deficits. Our biochemical data showed that EE-induced neuroprotection occurs in combination with multiple synergic neuroprotective pathways: (1) increased neurogenesis shown by an increase in BrdU-positive neurons; (2) diminished loss of dopaminergic neurons evidenced by upregulated tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels; (3) increased antioxidant capacity (e.g., CuZnSOD, CATALASE, GPX1/2, HO-1, DJ1 and PRXIII); and (4) enhanced autophagy (LC3 II, p62, BECLIN1, BNIP3, LAMP2, CATHEPSIN L and TFEB). Our study suggests that EE-induced multiple synergic protective pathways including enhanced neurogenesis, antioxidative capacity, and concordant autophagy promotion contribute to restoration of impaired dopaminergic neuronal function caused by PD. Thus, PD patients should be encouraged to actively participate in regular EE as a potent nonpharmacological therapeutic strategy against PD.

Correction to: Potential signaling pathways of acute endurance exercise-induced cardiac autophagy and mitophagy and its possible role in cardioprotection.

The article Potential signaling pathways of acute endurance exercise-induced cardiac autophagy and mitophagy and its possible role in cardioprotection, written by Youngil Lee.

Potential signaling pathways of acute endurance exercise-induced cardiac autophagy and mitophagy and its possible role in cardioprotection.

Cardiac myocytes are terminally differentiated cells and possess extremely limited regenerative capacity; therefore, preservation of mature cardiac myocytes throughout the individual's entire life span contributes substantially to healthy living. Autophagy, a lysosome-dependent cellular catabolic process, is essential for normal cardiac function and mitochondria maintenance. Therefore, it may be reasonable to hypothesize that if endurance exercise promotes cardiac autophagy and mitochondrial autophagy or mitophagy, exercise-induced cardiac autophagy (EICA) or exercise-induced cardiac mitophagy (EICM) may confer propitious cellular environment and thus protect the heart against detrimental stresses, such as an ischemia-reperfusion (I/R) injury. However, although the body of evidence supporting EICA and EICM is growing, the molecular mechanisms of EICA and EICM and their possible roles in cardioprotection against an I/R injury are poorly understood. Here, we introduce the general mechanisms of autophagy in an attempt to integrate potential molecular pathways of EICA and EICM and also highlight a potential insight into EICA and EICM in cardioprotection against an I/R insult.

Physical Fitness of Police Academy Cadets: Baseline Characteristics and Changes During a 16-Week Academy.

Police academies traditionally emphasize the importance of being physically fit. The purpose of this research was to determine cadet baseline physical fitness characteristics and assess effectiveness of a 16-week training program. Sixty-eight cadets (61 men, 7 women) volunteered to have baseline physical fitness characteristics assessed, and 55 cadets (49 men, 6 women) completed further testing at weeks 8 and 16. The testing comprised hand grip (strength), arm crank (upper-body power), 30 seconds Wingate (lower body power), sum of skinfolds and percentage body fat (body composition), 40-yard dash (sprint speed), 1 repetition maximum bench press (strength), T-test (agility), and sit-and-reach (flexibility). In addition, cadets completed standardized state testing (push-ups, sit-ups, vertical jump, and half-mile shuttle run). The training program consisted of 1 hour sessions, 3 d·wk, including aerobic, plyometrics, body weight, and resistance exercise. Significant changes were found in agility (p < 0.01), upper-body and lower-body peak power (p ≤ 0.05), sit-ups (p < 0.01), push-ups (p ≤ 0.05) across the first 8 weeks, and in agility (p ≤ 0.05), lower-body peak power (p ≤ 0.05), sit-ups (p < 0.01), push-ups (p ≤ 0.05), half-mile shuttle run (p < 0.01) across the full 16 weeks. However, none of the variables showed significant change across the second half of the program (weeks 8-16). A number of individual parameters of physical fitness showed evidence of improvement in the first 8 weeks, whereas none of the variables showed significant improvement in the second 8 weeks. This suggests modifications could be made to increase overall effectiveness of cadet physical training specifically after the 8-week mark.

Effects of long-term resistance exercise training on autophagy in rat skeletal muscle of chloroquine-induced sporadic inclusion body myositis.

PURPOSE: We examined whether resistance exercise training restores impaired autophagy functions caused by Chloroquine (CQ)-induced Sporadic Inclusion Body Myositis (sIBM) in rat skeletal muscle. METHODS: Male wistar rats were randomly assigned into three groups: Sham (n = 6), CQ (n = 6), and CQ + Exercise (CE, n = 6). To create a rat model of sIBM, rats in the CQ and CE group were intraperitoneally injected with CQ 5 days a week for 16 weeks. Rats in the CE group performed resistance exercise training 3 times a week for 8 weeks in conjunction with CQ starting from week 9 to week 16. During the training period, maximal carrying load, body weight, muscle weight, and relative muscle weight were measured. Autophagy responses were examined by measuring specific markers. RESULTS: While maximal carrying capacity for resistance exercise training was dramatically increased in the CE group, no significant changes occurred in the skeletal muscle weight as well as in the relative muscle weight of CE compared to the other groups. CQ treatment caused significant increases in the levels of Beclin-1 and p62, and decreases in the levels of LAMP-2 proteins. Interestingly, no significant differences in the LC3-II/I ratio or the LC3-II protein levels were observed. Although CQ-treatment groups suppressed the levels of the potent autophagy inducer, BNIP3, p62 levels were decreased in only the CE group. CONCLUSION: Our findings demonstrate that sIBM induced by CQ treatment results in muscle degeneration via impaired autophagy and that resistance exercise training improves movable loading activity. Finally, regular exercise training may provide protection against sIBM by enhancing the autophagy flux through p62 protein.

Effects of 4:1 carbohydrate/protein solution versus a carbohydrate-alone solution on IL-6, TNF-α, and cortisol during prolonged cycling in hot environmental conditions.

PURPOSE: Intense or prolonged exercise and/or heat stress might affect the immune system creating a response similar to trauma or inflammation, resulting in an increase in the susceptibility to viral infections. For example, during prolonged exercise, inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and the stress hormone cortisol are produced and released. Although there have been several studies examining the effects of nutritional supplementation on cytokine release in elite athletes, few studies have investigated the effects of different energy drinks during exercise in adverse environmental conditions. Therefore, the purpose of this study was to compare plasma levels of inflammatory cytokines TNF-α and IL-6, and the stress hormone cortisol, during prolonged cycling under hot environmental conditions while ingesting fluid that contains a ratio of 4:1 carbohydrates and protein (4:1 CHO/PRO) versus a carbohydrate-only drink (CHO). METHODS: Six male cyclists (aged 27 ± 8 years; weight 75.5 ± 3.4 kg; VO2max = 66 ± 2.7 mL/kg/min, mean ± standard error) rode on a stationary ergometer on two separate sessions for 2.5 hours at 75% VO2max in an environmental chamber set at 35°C and 60% relative humidity. During the first session the cyclists were given 4 mL/kg body weight of a 6% carbohydrate solution every 15 minutes. During the second session they were given 4 mL/kg body weight of a 4:1 carbohydrate/protein drink every 15 minutes. Subjects were not aware of which drink they were given in each trial. Blood samples were taken pre-, immediately post-, and 12 hours post-exercise. SPSS (IBM Corp, Armonk, NY) was utilized to analyze data through repeated measures analysis of variance. RESULTS: No significant main effect was observed between treatments in either cortisol (P = 0.97), IL-6 (P = 0.64), or TNF-α (P = 0.37) responses. Total cortisol concentrations were significantly elevated (P < 0.05) immediately post-exercise, and from pre- to 12 hours post-exercise with both the 4:1 CHO/PRO and the CHO-alone solutions. TNF-α concentrations were only significantly (P = 0.045) elevated post-exercise with the CHO-alone solution. A significant (P < 0.05) elevation of IL-6 was seen immediately post-exercise and 12 hours post-exercise with both the CHO-alone and 4:1 CHO/PRO solutions. CONCLUSIONS: Consuming a 4:1 CHO/PRO solution during prolonged cycling under hot environmental conditions has comparable effects on inflammatory cytokines to drinking a CHO-alone solution.

A comparison of cytokine responses during prolonged cycling in normal and hot environmental conditions.

PURPOSE: Components of immune function are affected by physical activity in an adverse environment. The purpose of this study was to compare plasma differences in inflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), in addition to the stress hormone cortisol, during prolonged cycling under normal and hot environmental conditions in elite cyclists. METHODS AND DESIGN: Six trained elite male cyclists (27 ± 8 years; 75.5 ± 4 kg; maximum oxygen uptake [VO2max] = 66 ± 6 mL/kg/min, mean ± SD). The cyclists biked for 2.5 h at their prescribed 60% maximum exercise workload (Wmax) or 75% VO2max either in an environmental chamber set at 15°C and 40% relative humidity (NEUTRAL) or at 35°C and 40% relative humidity (HOT). The cyclists were given 4 mL of water/kg body weight every 15 min under both conditions. RESULTS: Total cortisol concentrations were elevated (P < 0.05) immediately postexercise and 12 h postexercise in both the NEUTRAL and HOT conditions. TNF-α concentrations were only significantly (P = 0.045) elevated postexercise in HOT conditions. During the HOT conditions, a significant (P = 0.006 and 0.007, respectively) difference in IL-6 was seen immediately after and 12 h postexercise. During the NEUTRAL condition, IL-6 was only significantly elevated postexercise (P < 0.05). CONCLUSIONS: Heat exposure during a long bout of exercise is sufficient to elicit stress response in elite cyclists. However, the degree of release of anti-inflammatory and proinflammatory cytokines might be related to several factors that include the athlete's fitness level, hydration status, exercise intensity, and length of exposure to hot environments.

Intertester reliability of brachial artery flow-mediated vasodilation using upper and lower arm occlusion in healthy subjects.

The assessment of endothelial function as brachial artery flow-mediated vasodilatation is a widely used technique that determines the effect of risk factor intervention and may have the potential to predict the clinical benefit of antiatherogenic therapy. Previous studies suggest that flow-mediated dilation is greater using the upper-arm occlusion technique, but no data are available to compare intertester reliability between technicians. This study was undertaken to compare the amount of hyperemia between upper and lower occlusion techniques and to determine reproducibility between testers. Nineteen healthy adults, ages 25 to 50, were included in the study. Brachial artery vasodilatation was measured 1 and 3 minutes post cuff deflation and was compared with the baseline and expressed as a percent change. There was a tester effect in the percent change in diameter across all measurements. The results of this study reveal inconsistencies between testers when using a blood pressure cuff to induce hyperemia for the assessment of endothelial function through brachial artery flow-mediated vasodilation. However, upper arm as compared to lower arm blood pressure cuff occlusion results in significantly greater hyperemia and vasodilatation, even though there was a difference in measurements between testers.

The acute effect of aerobic exercise on brachial artery endothelial function in renal transplant recipients.

This study compared the effect of a 30-minute walk on brachial artery endothelial vasodilatation in kidney transplant (KT) recipients and healthy controls (HCs). Endothelial-dependent vasodilatation was measured by ultrasound before and after exercise. The HCs experienced a significant increase in vasodilatation after exercise 1 minute postocclusion when compared with the KT recipients (22%+/-13% vs 3%+/-4%; P<.05). Also, the HCs had a significantly higher vasodilatation from pre-treadmill walk to post-treadmill walk (1 minute postocclusion) when compared with KT recipients (from 3%+/-6% to 22%+/-13% vs 1%+/-3% to 3%+/-4%; P<.05). This acute vasodilatory response observed in the HCs may be related to the immediate release of nitric oxide and the combined response to shear stress and exercise. The KT recipients had several coronary artery disease risk factors that may have adversely affected endothelial function.

Effects of physioball and conventional floor exercises on early phase adaptations in back and abdominal core stability and balance in women.

The purpose of this study was to compare the effects of 5 weeks of physioball core stability and balance exercises with conventional floor exercises in women. The experimental group (n = 15) performed curl-ups and back extensions on the physioball while the control group (n = 15) performed the same exercises on the floor. Baseline and post-training tests included electromyography (EMG) recordings of the rectus abdominus and erector spinae muscles; abdominal, back, and knee strength measurements with the Cybex Norm System; and 2 unilateral stance balance tests. The physioball group was found to have significantly greater mean change in EMG flexion and extension activity (p = 0.04 and p = 0.01, respectively) and greater balance scores (p < 0.01) than the floor exercise group. No significant changes (p > 0.05) were observed for heart rate or Cybex strength measurements. Early adaptations in a short-term core exercise program using the physioball resulted in greater gains in torso balance and EMG neuronal activity in previously untrained women when compared to performing exercises on the floor.