Enhancing brain health: Swimming-induced BDNF release and epigenetic influence in MS female mouse models.

Multiple sclerosis (MS) is a condition characterized by inflammation in the central nervous system (CNS), impacting sensory, motor, and cognitive abilities. Globally, around three million individuals are affected by MS, with up to 97,000 cases in Iran attributed to genetic predispositions along with various environmental factors like smoking. Cognitive impairment affects a significant portion of patients, ranging from 45% to 70%. This study investigates the impact of regular aerobic swimming exercise for four weeks, mild cognitive impairment induced by encephalomyelitis, and their combination on the expression of microRNA-142-3p and its correlation with the release of brain-derived neurotrophic factor (BDNF) in relation to spatial memory. Twenty-one C57BL/6 mice were divided into three groups. RT-PCR was used for microRNA expression analysis, and BDNF levels were assessed via western blotting. Clinical scores and animal weights were monitored daily. EAE induction led to an increase in microRNA-142-3p expression and a decrease in BDNF levels compared to the control group. Exercise inversed them significantly, and improved spatial memory. Our findings indicate that engaging in regular swimming exercise can counteract the up-regulation of miR-142-3p in brain tissue, which likely contributes to mild cognitive impairment induced by MS. Additionally, the increase in BDNF following exercise appears to be associated with miR-142-3p and the enhancement of cognitive function. Thus, the therapeutic benefits of exercise, particularly in releasing BDNF to improve cognitive function in MS patients, warrant consideration. Lifestyle modifications have the potential to effectively modulate environmental influences and ethnicity, underscoring their significance in MS management.

Ameliorating effect of 6-week swimming exercise on mice with experimental autoimmune encephalomyelitis (EAE) by reducing fetuin-A and increasing AMPK & NAD⁺ levels in liver tissue.

Objectives: Multiple sclerosis (MS) is a chronic inflammatory disease affecting sensory and motor function in the central nervous system. Physical activities in the prevention and treatment of such conditions have shown promising results. However, their mechanisms of action have not been fully known yet and need further study. The present study aimed to evaluate the preventive effect of swimming exercise on some liver factors involved in inflammation and MS. Materials and Methods: In this study, experimental autoimmune encephalomyelitis was induced in C57BL/6 mice, and the effect of a 6-week swimming exercise on the levels of fetuin-A, AMP-activated protein kinase (AMPK), and Nicotinamide adenine dinucleotide (NAD+) in their liver tissue was investigated by western blot analysis and NAD+ colorimetric assay. Results: The study showed that EAE induction substantially (3.5 - fold) enhanced the fetuin-A levels and caused a reduction in AMPK and NAD+ amount. This is when doing 6 weeks of swimming exercise reduced fetuin-A to slightly above control. Also, levels of AMPK and NAD+ markedly increased in C57BL/6 mice with EAE. Conclusion: Doing regular exercise may limit the body's inflammatory responses and reduce the severity of MS by regulating the expression of fetuin-A and increasing AMPK and NAD⁺ levels in liver tissue.

Lack of Evidence for Crossover Fatigue with Plantar Flexor Muscles.

The occurrence and mechanisms underlying non-local or crossover muscle fatigue is an ongoing issue. This study aimed to investigate crossover fatigue of the plantar flexor muscles. Sixteen recreationally active males (n = 6) and females (n = 10) visited the laboratory for four sessions and performed a single 5-s pre-test maximal voluntary isometric contraction (MVIC) with each plantar flexors muscle. Thereafter, the fatigue intervention involved two 100-s MVICs (60-s recovery) with their dominant plantar flexors or rested for 260-s (control). Subsequently, in two separate sessions, Hoffman reflexes (H-reflex) were evoked in the non-dominant, non-exercised, leg before and following the dominant leg fatigue or control intervention (Fatigue-Reflex and Control-Reflex conditions). MVIC forces and volitional (V)-waves were monitored in the non-dominant leg in the other two sessions (Fatigue-MVIC and Control-MVIC) before and after the intervention (fatigue or control) as well as during 12 repeated MVICs and immediately thereafter. Despite the force reduction in the dominant leg (42.4%, p = 0.002), no crossover force deficit with single (F(1,9) = 0.02, p = 0.88, pƞ2 = 0.003) or repeated (F(1,9) = 0.006, p = 0.93, pƞ2 = 0.001) MVIC testing were observed. The H-reflex did not change after the fatigue (F(1,7) = 0.51; p = 0.49; pƞ2 = 0.06) or repeated MVICs (F(1,8) = 0.27; p = 0.61; pƞ2 = 0.03). There were also no crossover effects of fatigue on the V-wave with single (F(1,8) = 3.71, p = 0.09, pƞ2 = 0.31) or repeated MVICs (F(1,6) = 1.45, p = 0.27, pƞ2 = 0.19). Crossover fatigue was not evident with the plantar flexors nor any significant changes in H-reflex and V-waves in the soleus muscle. This finding suggests that crossover fatigue may not necessarily occur in slow-twitch predominant muscle groups.

Gene expression of angiogenesis and apoptotic factors in female BALB/c mice with breast cancer after eight weeks of aerobic training.

OBJECTIVES: Breast cancer is the most common cancer in women, caused by a disorder in the angiogenesis and apoptosis process. Exercise can affect the process of angiogenesis and apoptosis in the tumor tissue. Thus, the aim of the present study was to investigate the changes in angiogenesis and apoptotic factors in mice with breast cancer after 8 weeks of exercise training. MATERIALS AND METHODS: Sixteen females BALB/c mice (age: 3-5 weeks and weight: 17.1 ± 0.1 g) with breast cancer were randomly divided into two groups of aerobic training and control. The aerobic training included 8 weeks and 5 sessions per week of running with an intensity of 14-20 m.min-1. HIF-1α, VEGF, miR-21 and cytochrome C, Apaf-1, caspase-9, and caspase-3 gene expressions were examined by real-time PCR. Repeated measures ANOVA, Bonferroni's post hoc test, and independent samples t-test were used to analyze the data (P<0.05). RESULTS: The results showed that aerobic training reduced the growth of tumor volume and significantly reduced miR-21 gene expression. Aerobic training also significantly increased the gene expression of HIF-1α, cytochrome C, Apaf-1, caspase-9, and caspase-3, while changes in VEGF gene expression were not statistically significant. CONCLUSION: It appears that aerobic exercise training reduces tumor size and ameliorates breast cancer by reducing miR-21 gene expression, suppressing the apoptosis process, and reducing angiogenesis.

Voluntary wheel running stimulates the expression of Nrf-2 and interleukin-10 but suppresses interleukin-17 in experimental autoimmune encephalomyelitis.

Multiple sclerosis is an inflammatory and neurodegenerative disease of the central nervous system in which the immune cells attack the myelin sheath of the nerves, leading to axonal damage, inflammation, immune cell infiltration, and demyelination of the brain and spinal cord. These detrimental changes cause some impairments, such as depression, motor deficit, and cognitive dysfunction, affecting the quality of life in MS patients and their social activities. The present study assessed the impact of 6-week voluntary exercise prior to disease onset on the expression of Nrf-2, IL-10, IL-17, as well as the degree of lymphocyte infiltration in the spinal cord and disease severity in the chronic period of the EAE (30 days post-induction). The results showed that voluntary wheel running stimulated the expression of Nrf-2 and IL-10, while decreased the expression of IL-17, the rate of lymphocyte infiltration, and the severity of EAE at the chronic period of the disease. Thus, alterations in lifestyle, such as regular exercise, may modulate inflammation and disease severity in patients with MS.

The Role of Forced and Voluntary Training on Accumulation of Neural Cell Adhesion Molecule and Polysialic Acid in Muscle of Mice with Experimental Autoimmune Encephalomyelitis.

It has been suggested that depletion of adhesion molecules is one of the factors associated with or possibly responsible for multiple sclerosis (MS) progression. The aim of this study was to investigate the effect of forced and voluntary training before and after induction of experimental autoimmune encephalomyelitis (EAE) on accumulation of neural cell adhesion molecule (NCAM) and polysialic acid (PSA) in neuromuscular junction denervation in plantaris and soleus muscles in C57BL/6 female mice. A total of 40 female C57BL/6 mice, 10-week-old, were randomly divided into four groups, including induced control groups without EAE induction, induced EAE without training, and forced and voluntary training groups. Myelin oligodendrocyte glycoprotein peptide 35-55 (300 µg in saline; MOG 35-55; KJ Ross-Petersen ApS, Denmark) was injected subcutaneously at the base of the tail of each mouse. Clinical assessment of EAE was performed daily using a 15-point scoring system following immunization. Training groups performed the swimming program for 30 min/day, 5 times/week, for 4 weeks. Mice had access to a treadmill for one hour per day, 5times/week, for 4 weeks in individual cage. The mice were scarified, and the plantaris and soleus muscles were then isolated for investigation of proteins expression using IHC. An analysis of the preventive exercise (before) and recovery exercise (after) of the EAE was performed. Images of the stained sections were taken using a fluorescent microscope. Quantitative image analysis was performed using ImageJ software package. The obtained data from the mean percentage expression of PSA and NCAM in pre- and post-soleus and plantaris muscles showed that the highest and lowest expression levels of PSA and NCAM belonged to control and swim EAE (SE) groups, respectively. The low expression levels of PSA and NCAM were detected in rat with MS without intervention. In conclusion, the relationship between increasing levels of NCAM and PSA protein expression and voluntary and compulsory activity were detectable both in pre and post-soleus and plantaris. However, voluntary activity resulted in more expression levels of NCAM and PSA than that of compulsory. In conclusion, since it has been suggested that depletion of NCAM is one of the factors associated with or possibly responsible for MS progression, these findings show exercise MS progression may be reduced by increasing expression of exercise-related adhesion molecule such as NCAM and PSA (a glycan modification of the NCAM).

Exercise modulates the levels of growth inhibitor genes before and after multiple sclerosis.

Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system. The animal model of MS, experimental autoimmune encephalomyelitis (EAE), is commonly used for studies of human inflammatory demyelinating diseases and has been shown to be suitable for studying the effects of exercise on MS pathophysiology. The present study was conducted to determine the impact of forced swimming and voluntary running wheel exercises before and after the induction of EAE on expression of Nogo-A, NgR, and ROCK genes in the brain tissue. A total of 96 C57BL/6 mice were randomly divided into two groups, namely exercises before (EXb, n = 48) and after (EXa, n = 48) induction of EAE. Each group was divided into four subgroups: Forced Swimming + EAE (n = 12), Voluntary Running Wheel + EAE (n = 12), NoEX-EAE (n = 12), and Control group (n = 12). Animals performed either swimming exercise for 30 min per day or running wheel for one hour per day, five days per week for four weeks. Results of Luxal Fast Blue (LFB) staining demonstrated that the degree of demyelination was significantly less in the experimental exercised compared to NoEX-EAE groups (P < .05). Amazingly, both modes of exercise reduced the severity of MS symptoms in mice exposed to swimming and wheel running, evaluated as body weight, clinical scores, degree of demyelination, and gene expressions, regardless of whether the exercise was performed before or after EAE induction.

High-intensity interval training increase GATA4, CITED4 and c-Kit and decreases C/EBPß in rats after myocardial infarction.

AIM: Myocardial infarction (MI), an important cause of morbidity and mortality, can be followed by left ventricular dysfunction and cardiomyocyte loss. Cardiac repair mechanisms may subsequently improve left ventricular function. Exercise training has been suggested to have cardioprotective effects against MI damage, but detailed knowledge is lacking on the effects of different types and intensities of exercise training on molecular targets of cardiomyocyte regeneration. MAIN METHODS: MI was induced in male Wistar rats by ligating the left anterior descending coronary artery. After MI induction, the rats were randomly assigned to one of five groups: sham operated, and experimental MI followed by no exercise, or low, moderate or high intensity exercise Cardiac function and infarct size were assessed by echocardiography and Evans blue/TTC staining, respectively. The expression of mRNA markers and proteins associated with myocardial regeneration was measured with RT-PCR and western blotting. KEY FINDINGS: Exercise training at different intensities improved cardiac function and levels of stem cell and cardiomyocyte markers, and reduced infarct size. mRNA levels of GATA4, Nkx2.5 and c-Kit and protein expression of Nkx2.5 and c-Kit were significantly increased in all MI-exercise groups. The high-intensity exercise group had greater increases than the low and moderate intensity exercise groups. In the high-intensity exercise group, Sca-1 and CITED4 increased more than in the low-intensity exercise group. C/EBPß mRNA and protein levels decreased after exercise training, with greater reductions in the high-intensity exercise group than the low- or moderate-intensity groups. SIGNIFICANCE: The findings suggest that by targeting cardiogenesis, high-intensity training can exert cardioprotective effects against cardiac dysfunction in an experimental model of MI.

Overcoming the challenges of conventional dispersive liquid-liquid microextraction: analysis of THMs in chlorinated swimming pools.

A rapid, simple, and sensitive approach to the analysis of trihalomethanes (THMs) in swimming pool water samples has been developed. The main goal of this study was to overcome or to improve the shortcomings of conventional dispersive liquid-liquid microextraction (DLLME) and to maximize the realization of green analytical chemistry principles. The method involves a simple vortex-assisted microextraction step, in the absence of the dispersive solvent, followed by salting-out effect for the elimination of the centrifugation step. A bell-shaped device and a solidifiable solvent were used to simplify the extraction solvent collection after phase separation. Optimization of the independent variables was performed by using chemometric methods in three steps. The method was statistically validated based on authentic guidance documents. The completion time for extraction was less than 8 min, and the limits of detection were in the range between 4 and 72 ng L-1. Using this method, good linearity and precision were achieved. The results of THMs determination in different real samples showed that in some cases the concentration of total THMs was more than threshold values of THMs determined by accredited healthcare organizations. This method indicated satisfactory analytical figures of merit. Graphical Abstract A novel green microextraction technique for overcoming the challenges of conventional DLLME. The proposed procedure complies with the principles of green/sustainable analytical chemistry, comprising decreasing the sample size, making easy automation of the process, reducing organic waste, diminishing energy consumption, replacing toxic reagents with safer reagents, and enhancing operator safety.

Effects of Eight-week Resistance Training Program in Men With Multiple Sclerosis.

BACKGROUND: Muscle weakness and fatigue contribute to the reduction of daily activity in multiple sclerosis (MS) patients. Therapeutic strategies to promote improvements in muscle strength and endurance are limited in individuals with MS. Some evidence showed that exercise may improve and affect different aspects of the disease including quality of life, fatigue, motor and cognitive functions. OBJECTIVES: To investigate the value of resistance training of moderate to high intensity on motor function, muscle strength, balance and perceived disability in male patients with multiple sclerosis compared to a control group. PATIENTS AND METHODS: 20 male patients with MS (mean ± SD, age: 34.05 ± 7.8 y; Expanded Disability Status Scale (EDSS): 2.94 ± 1.5) were recruited and randomized either to the exercise (E) or control group (C). Group E participated in a three-time weekly individualized progressive resistance-training program (both upper and lower extremities) for eight weeks, while group C was advised not to change their physical activity habits. All initial measures (including EDSS, balance, muscle strength, and functional mobility) were re-evaluated at the end of the program. RESULTS: Two patients of group E left the program. The other eight subjects completed the program with no MS-related exacerbations/complications. There was a significant change in 2 of 3 aspects of ambulatory function [Three minutes step test (P = 0.001), Timed Up and Go test (P = 0.009)], muscle strength (P = 0.000), and EDSS (P = 0.014). Comparing the two groups, we did not observe any significant change in "Balance" (P = 0.407). CONCLUSIONS: The resistance training of moderate to high intensity was well-tolerated in MS patients and may be an effective intervention for improving muscle strength, functional ability and EDSS-based disease severity.

The Effects of Rope Training on Lymphocyte ABCA1 Expression, Plasma ApoA-I and HDL-c in Boy Adolescents.

BACKGROUND: Early obesity and its transfer to the adulthood, increases likelihood incidence of coronary artery disease (CAD). ATP-binding cassette transporter (ABCA1) as a member of the ABC transporters family plays a crucial role in reverse cholesterol transport and CAD prevention. OBJECTIVE: The current study aimed to investigate ABCA1 expression in lymphocytes, plasma apolipoprotein A-I and HDL-C in response to eight-week interval endurance rope training in overweight and obese boy adolescents. PATIENTS AND METHODS: Thirty students (17.3 ± 1.1 yr, 85.73 ± 11.68 kg and 28.41 ± 2.36 kg / m²) volunteered and were randomly assigned into training (n= 15) and control (n = 15) groups. Exercise protocol was interval endurance rope training (8 wk, 4 d/wk and 40 min/d). Cell hemolysis and sensitive Elisa method was used for Lymphocyte ABAC1 protein expression.t-test was employed. RESULTS: The independent-samples T-Test results showed that after 8 weeks IERT, the levels of lymphocyte ABCA1 expression (P = 0/001) and VO2max(P = 0/001) significantly increased and plasma levels of TG (P = 0.017), TC (P = 0.001), LDL-c/HDL-c (P = 0.026),TC/HDL-c (P = 0.002) and measures of BF% (P = 0/015) and BMI (P = 0.042) as anthropometric indicators significantly decreased. Changes of other variables such as increase in ApoA-I, HDL-c and decrease in LDL-c, body weight, were not significant. CONCLUSIONS: The findings of this study proved that eight-week interval endurance rope training can have positive effects on lymphocyte ABCA1 protein expression (as gatekeeper of reverse cholesterol process) and lipid profiles among overweight and obese boy adolescents.

Effect of treadmill running on the expression of genes that are involved in neuronal differentiation in the hippocampus of adult male rats.

Gene expression in the rodent brain is dependent on exercise. However, our findings regarding this fact are inadequate. The aim of this study was to evaluate the effect of exercise intensity on changes in factors involved in neuronal differentiation and plasticity in the hippocampus of adult male rats. Thus, the effects of 2 weeks treadmill running at of low (11 m/min) and high (25 m/min) intensities, 30 min/day for 14 consecutive days on the expression of two genes, microRNA-124 and neuron restrictive silencer factor/RE1-silencing transcription factor (REST) as well as changes of two proteins of brain-derived eurotrophic factor (BDNF) and tyrosine kinase B (TrkB) were analysed. Using quantitative real-time PCR techniques have shown that both exercise intensities reduced the expression of REST (31% in low exercise intensity, 52% in high exercise intensity) and elevated the expression of miR-124 (3.8-fold in low exercise intensity, 11.9-fold in high exercise intensity)significantly (P≤0.05). This suggests that exercise probably through the changes in these genes is involved in neuronal differentiation in the hippocampus of rats. BDNF and TrkB levels were measured by ELISA. Exercise, at low intensity, increased TrkB (4.51 ng/L vs. 3.73 ng/L) and BDNF (11.97 ng/L vs. 11.08 ng/L) proteins significantly (P≤0.05), while at high intensity,the changes in comparison with the control group were not significant. Expression levels during the exercise programme with high intensity were dramatic for miR-124 and less dramatic for REST compared with low intensity exercise programme.

Effect of combination exercise training on metabolic syndrome parameters in postmenopausal women with breast cancer.

CONTEXT: Studies have shown that physical activity or exercise training may decrease the metabolic syndrome. AIM: The aim of the present study is to clarify the effect of combination exercise training on metabolic syndrome parameters in postmenopausal women with breast cancer. SETTING AND DESIGN: Twenty nine postmenopausal women (58.27 +/- 6.31 years) with breast cancer were divided into two groups randomly as experimental group (n=14) and control group (n=15). MATERIALS AND METHODS: Subjects of experimental group were performed 15 weeks combination exercise training including walking (2 sessions per week) and resistance training (2 sessions per week that was different from walking days). Before and after 15 weeks, fasting insulin and glucose, insulin resistance, high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) were calculated. Also, Vo2peak, rest heart rate (RHR), systolic blood pressure (SBP), body weight (BW), body mass index (BMI) and waist to hip ratio (WHR) were measured in two groups. STATISTICAL ANALYSIS USED: Mean values of two groups in pre and post test were compared by independent and paired t-test for all measurements (P ≤ 0.05). RESULTS: Significant differences were observed for VO2peak, RHR, BW, BMI, WHR, SBP, fasting insulin and glucose, HDL-C and TG between experimental and control groups after 15 weeks (P< 0.05). CONCLUSIONS: Combination exercise training can improve metabolic syndrome parameters in postmenopausal women with breast cancer.

Combined exercise training reduces IFN-γ and IL-17 levels in the plasma and the supernatant of peripheral blood mononuclear cells in women with multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder in which lymphocytic infiltration mediated mainly by pro-inflammatory cytokines. In this study, we examined the effect of combined exercise training on the levels of IFN-γ, IL-4 and IL-17 in the plasma and the supernatant of peripheral blood lymphocytes in women with multiple sclerosis. Expanded Disability Status Scale (EDSS), VO(2)max, muscle strength, and balance tests were obtained at baseline and post-treatment follow-up. Combined exercises training was designed for 24 sessions during 8 weeks. Each session was started with 5 min warm-up and was followed by 10 min stretch training, 20 min aerobic exercises and 20 min resistance-endurance training. The disability score was significantly decreased in test MS subjects after 8 weeks combined exercise training. Muscle strength and balance were increased significantly after the training program in test group. In this study, plasma, and peripheral blood mononuclear cell (PBMC) IL-17 and IFN-γ production was significantly decreased after 8 weeks combined training. Our findings suggest that combined training has useful anti-inflammatory effects by decrease in PBMC and plasma IL-17 production.