Spinal cord abnormal autophagy and mitochondria energy metabolism are modified by swim training in SOD1-G93A mice.

Amyotrophic lateral sclerosis (ALS) may result from the dysfunctions of various mechanisms such as protein accumulation, mitophagy, and biogenesis of mitochondria. The purpose of the study was to evaluate the molecular mechanisms in ALS development and the impact of swim training on these processes. In the present study, an animal model of ALS, SOD1-G93A mice, was used with the wild-type mice as controls. Mice swam five times per week for 30 min. Mice were analyzed before ALS onset (70 days old), at ALS 1 disease onset (116 days old), and at the terminal stage of the disease ALS (130 days old), and compared with the corresponding ALS untrained groups and normalized to the wild-type group. Enzyme activity and protein content were analyzed in the spinal cord homogenates. The results show autophagy disruptions causing accumulation of p62 accompanied by low PGC-1α and IGF-1 content in the spinal cord of SOD1-G93A mice. Swim training triggered a neuroprotective effect, attenuation of NF-l degradation, less accumulated p62, and lower autophagy initiation. The IGF-1 pathway induces pathophysiological adaptation to maintain energy demands through anaerobic metabolism and mitochondrial protection. KEY MESSAGES: The increased protein content of p62 in the spinal cord of SOD1-G93A mice suggests that autophagic clearance and transportation are disrupted. Swim training attenuates neurofilament light destruction in the spinal cord of SOD1-G93A mice. Swim training reducing OGDH provokes suppression of ATP-consuming anabolic pathways. Swim training induces energy metabolic changes and mitochondria protection through the IGF-1 signaling pathway.

Combined probiotics with vitamin D3 supplementation improved aerobic performance and gut microbiome composition in mixed martial arts athletes.

Introduction: Mixed Martial Arts (MMA) is characterized as an interval sport in which the training program focuses on enhancing both aerobic and anaerobic capacities. Therefore, strategies targeting the intestinal microbiome may be beneficial for MMA athletes. Moreover, vitamin D supplementation may amplify the positive effects of certain bacterial strains. We previously demonstrated that the combined of probiotics and vitamin D3 supplementation improved the lactate utilization ratio, total work, and average power achieved during anaerobic tests in MMA. Therefore, this study aimed to investigate whether combined probiotic and vitamin D3 ingestion can modify the composition of the gut microbiome and epithelial cell permeability, influence the inflammatory response, and ultimately enhance aerobic capacity. Methods: A 4-week clinical trial was conducted with 23 male MMA athletes randomly assigned to either the probiotic + vitamin D3 (PRO + VIT D) group or the vitamin D3 group (VIT D). The trial employed a double-blind, placebo-controlled design and involved measurements of serum inflammatory markers, gut microbiome composition, epithelial cell permeability, and aerobic performance. Results: After 4-week of supplementation, we found a significantly lower concentration of calprotectin in the PRO + VIT D group (34.79 ± 24.38 mmol/L) compared to the value before (69.50 ± 46.91) supplementation (p = 0.030), augmentation of beta diversity after the intervention in the PRO + VIT D group (p = 0.0005) and an extended time to exhaustion to 559.00 ± 68.99; compared to the value before (496.30 ± 89.98; p = 0.023) after combined probiotic and vitamin D3 supplementation in MMA athletes. No effect was observed in the VIT D group. Conclusion: Our results indicate that combined treatment of probiotics and vitamin D3 may cause alterations in alpha and beta diversity and the composition of the gut microbiota in MMA athletes. We observed an improvement in epithelial cell permeability and an extended time to exhaustion during exercise in MMA athletes following a 4-week combined probiotic and vitamin D3 treatment.

Impact of 12 Weeks of Vitamin D3 Administration in Parkinson's Patients with Deep Brain Stimulation on Kynurenine Pathway and Inflammatory Status.

The current study aimed to investigate whether a 12-week Body Mass Index (BMI)-based (the higher the BMI, the higher the dosage) vitamin D3 administration may affect both the kynurenine pathway (KP) and the inflammatory state in Parkinson's disease (PD) patients with deep brain stimulation (DBS) and may be useful for developing novel therapeutic targets against PD. Patients were randomly assigned to two groups: supplemented with vitamin D3 (VitD, n = 15) and treated with vegetable oil (PL, n = 21). Administration lasted for 12 weeks. The isotope dilution method by LC-MS/MS was applied to measure KP and vitamin D metabolites. Serum concentrations of cytokines such as IL-6 and TNF-α were measured using ELISA kits. After administration, the serum concentration of TNF-α decreased in PD patients with DBS. Moreover, in KP: 3-hydroksykynurenine (3-HK) was increased in the PL group, picolinic acid was decreased in the PL group, and kynurenic acid tended to be higher after administration. Furthermore, a negative correlation between 3-HK and 25(OH)D3 and 24,25(OH)2D3 was noticed. Our preliminary results provide further evidence regarding a key link between the KP substances, inflammation status, and metabolites of vitamin D in PD patients with DBS. These findings may reflect the neuroprotective abilities of vitamin D3 in PD patients with DBS.

Effect of 12-Week BMI-Based Vitamin D3 Supplementation in Parkinson's Disease with Deep Brain Stimulation on Physical Performance, Inflammation, and Vitamin D Metabolites.

Parkinson's disease (PD) is the second most common neurodegenerative disease. To manage motor symptoms not controlled adequately with medication, deep brain stimulation (DBS) is used. PD patients often manifest vitamin D deficiency, which may be connected with a higher risk of falls. We administered a 12-week vitamin D3 supplementation based on BMI (with higher doses given to patients with higher BMI) to investigate its effects on physical performance and inflammation status in PD patients with DBS. Patients were randomly divided into two groups: treated with vitamin D3 (VitD, n = 13), and supplemented with vegetable oil as the placebo group (PL, n = 16). Patients underwent functional tests to assess their physical performance three times during this study. The serum 25(OH)D3 concentration increased to the recommended level of 30 ng/mL in the VitD group, and a significant elevation in vitamin D metabolites in this group was found. We observed significant improvement in the Up and Go and the 6 MWT in the VitD group. In inflammation status, we noticed a trend toward a decrease in the VitD group. To conclude, achieving the optimal serum 25(OH)D3 concentration is associated with better functional test performance and consequently may have a positive impact on reducing falling risk in PD.

Effects of Probiotics and Vitamin D3 Supplementation on Sports Performance Markers in Male Mixed Martial Arts Athletes: A Randomized Trial.

BACKGROUND: Strategies targeted at the intestine microbiome seem to be beneficial for professional athletes. The gut-muscle axis is associated with the inflammatory state, glucose metabolism, mitochondrial function, and central nervous system health. All these mechanisms may affect maximal oxygen uptake, muscle strength, and training adaptation. Moreover, the positive effect of certain bacterial strains may be enhanced by vitamin D. Thus, this study aimed to assess and compare the level of selected markers of sports performance of mixed martial arts (MMA) athletes supplemented with vitamin D3 or probiotics combined with vitamin D3. METHODS: A 4-week randomized double-blind placebo-controlled clinical trial was conducted with 23 MMA male athletes assigned to the vitamin D3 group (Vit D; n = 12) or probiotics + vitamin D3 group (PRO + VitD; n = 11). Repeated measures of the creatine kinase level, lactate utilization ratio, and anaerobic performance were conducted. RESULTS: After 4 weeks of supplementation, we found lower lactate concentrations 60 min after the acute sprint interval in the PRO + VitD group when compared to the Vit D group (4.73 ± 1.62 and 5.88 ± 1.55 mmol/L; p < 0.05). In addition, the intervention improved the total work (232.00 ± 14.06 and 240.72 ± 13.38 J kg-1; p < 0.05), and mean power following the anaerobic exercise protocol (7.73 ± 0.47 and 8.02 ± 0.45 W kg-1; p < 0.05) only in the PRO + VitD group. Moreover, there was an improvement in the lactate utilization ratio in the PRO + VitD group compared with the Vit D group as shown by the percentage of T60/T3 ratio (73.6 ± 6.9 and 65.1 ± 9.9%, respectively; p < 0.05). We also observed elevated serum 25(OH)D3 concentrations after acute sprint interval exercise in both groups, however, there were no significant differences between the groups. CONCLUSION: Four weeks of combined probiotic and vitamin D3 supplementation enhanced lactate utilization and beneficially affected anaerobic performance in MMA athletes.

Swim Training Ameliorates Hyperlocomotion of ALS Mice and Increases Glutathione Peroxidase Activity in the Spinal Cord.

(1) Background: Amyotrophic lateral sclerosis (ALS) is an incurable, neurodegenerative disease. In some cases, ALS causes behavioral disturbances and cognitive dysfunction. Swimming has revealed a neuroprotective influence on the motor neurons in ALS. (2) Methods: In the present study, a SOD1-G93A mice model of ALS were used, with wild-type B6SJL mice as controls. ALS mice were analyzed before ALS onset (10th week of life), at ALS 1 onset (first symptoms of the disease, ALS 1 onset, and ALS 1 onset SWIM), and at terminal ALS (last stage of the disease, ALS TER, and ALS TER SWIM), and compared with wild-type mice. Swim training was applied 5 times per week for 30 min. All mice underwent behavioral tests. The spinal cord was analyzed for the enzyme activities and oxidative stress markers. (3) Results: Pre-symptomatic ALS mice showed increased locomotor activity versus control mice; the swim training reduced these symptoms. The metabolic changes in the spinal cord were present at the pre-symptomatic stage of the disease with a shift towards glycolytic processes at the terminal stage of ALS. Swim training caused an adaptation, resulting in higher glutathione peroxidase (GPx) and protection against oxidative stress. (4) Conclusion: Therapeutic aquatic activity might slow down the progression of ALS.