Global Histone H4 Acetylation in the Olfactory Bulb of Lactating Rats with Different Patterns of Maternal Behavior.

In rats, variations in the levels of neuromodulatory molecules and in the expression of their receptors are observed during pregnancy and postpartum. These changes may contribute to the development and management of maternal behavior. The frequency of licking the pups is used to evaluate maternal care, having mothers with low licking (LL) and high licking (HL) frequencies. Previously, we found that HL had increased levels of transcriptional expression of the receptors for serotonin (HTR1a, HTR1b), estrogen (Erα), dopamine (D1a), and prolactin (Prlr) than LL in the olfactory bulb (OB); however, the molecular mechanisms behind this phenomenon are unknown. Since evidences pointed out that epigenetic marks, which may alter gene expression, are modulated by environmental factors such as exercise, diet, maternal care, and xenobiotic exposure, our objective was to verify the acetylation levels of histone-H4 in the OB of LL and HL rats. Maternal behavior was studied for the first 7 postpartum days. LL (n = 4) and HL (n = 5) mothers were selected according to the behavior of licking their pups. Acetylation levels of histone-H4 were determined using the Global Histone-H4 Acetylation Assay Kit and expressed as ng/mg protein (mean ± SD). Analysis revealed that HL (278.36 ± 68.95) had increased H4 acetylation levels than LL (183.24 ± 73.05; p = 0.045). The enhanced expression of the previously studied receptors in the OB could be related, at least in part, to the hyperacetylation status of histone-H4 here observed. Afterward, the modulation of histone acetylation levels could exert a pivotal role through molecular mechanisms involved in the different patterns of maternal behavior.

Treadmill exercise alters histone acetylation differently in rats exposed or not exposed to aversive learning context.

Epigenetic modifications have been linked to memory formation after learning context exposure and to exercise effects on memory performance. The aim of this study was to investigate the effect of treadmill exercise (20 min/day during 2 weeks) on H3K14 acetylation and H3S10 phosphorylation levels in the hippocampi of 3-month-old Wistar rats exposed and not exposed to aversive learning context. Male Wistar rats aged 2-3 months were assigned to non-exercised (sedentary) and exercised (running daily for 20 min for 2 weeks) groups. Single-trial step-down inhibitory avoidance (IA) conditioning was employed as an aversive memory model. Epigenetic parameters were determined 30 min after the IA test. A decrease in the H3K14 acetylation in the hippocampus 24 h after IA training (30 min after test session) was observed. Exercise reversed the IA effect, and no effect was observed in the non-IA exposed group. Our data support the hypothesis that modulation of H3K14 acetylation levels in the hippocampus might be related, at least in part, to exercise effects on aversive memory.

Treadmill exercise alters histone acetyltransferases and histone deacetylases activities in frontal cortices from wistar rats.

Studies have pointed out the relationship between neuroprotective exercise effects and epigenetic mechanisms on the hippocampus. Considering the role of frontal cortex on brain functions, we investigated the impact of different exercise protocols on enzymatic system involved with histone acetylation status, histone acetyltransferases (HATs), and histone desacetylases (HDACs) in frontal cortices from Wistar rats. Male Wistar rats aged 3 months were submitted to a single session or a daily running protocol during 2 weeks. The single session enhanced HAT activity, while the moderate daily exercise protocol reduced the HDAC activity. Our results indicate that frontal cortex is susceptible to epigenetic modulation following exercise and that both exercise protocols seem to induce a histone hyperacetylation condition in this brain area.

Treadmill exercise induces age-related changes in aversive memory, neuroinflammatory and epigenetic processes in the rat hippocampus.

It has been described that exercise can modulate both inflammatory response and epigenetic modifications, although the effect of exercise on these parameters during the normal brain aging process yet remains poorly understood. Here, we investigated the effect of aging and treadmill exercise on inflammatory and epigenetic parameters specifically pro and anti-inflammatory cytokines levels, activation of NF-kB and histone H4 acetylation levels in hippocampus from Wistar rats. Additionally, we evaluated aversive memory through inhibitory avoidance task. Rats of 3 and 20 months of age were assigned to non-exercised (sedentary) and exercised (running daily for 20 min for 2 weeks) groups. The effect of daily forced exercise in the treadmill was assessed. The levels of inflammatory and epigenetic parameters were determined 1h, 18 h, 3 days or 7 days after the last training session of exercise. It was observed an age-related decline on aversive memory, as well as aged rats showed increased hippocampal levels of inflammatory markers, such as TNFα, IL1-ß and NF-kB and decreased IL-4 levels, an anti-inflammatory cytokine. Moreover, lower levels of global histone H4 acetylation were also observed in hippocampi from aged rats. Interestingly, there was a significant correlation between the biochemical markers and the inhibitory avoidance test performance. The forced exercise protocol ameliorated aging-related memory decline, decreased pro-inflammatory markers and increased histone H4 acetylation levels in hippocampi 20-months-old rats, while increased acutely IL-4 levels in hippocampi from young adult rats. Together, these results suggest that an imbalance of inflammatory markers might be involved to the aging-related aversive memory impairment. Additionally, our exercise protocol may reverse aging-related memory decline through improving cytokine profile.

Exergame and/or conventional training-induced neuroplasticity and cognitive improvement by engaging epigenetic and inflammatory modulation in elderly women: A randomized clinical trial.

OBJECTIVE: To evaluate the acute and long-term impact of exergaming (EXE) and conventional therapy (CON) in the peripheral levels of brain-derived neurotrophic factor (BDNF), inflammatory markers (interleukin [IL]-1b, IL-6, IL-8, and tumor necrosis factor-alpha [TNF-α]) and epigenetic mechanisms (global histone H3 and H4 acetylation levels in mononuclear cells) of healthy elderly women. We also evaluated the effect of intervention on cognitive performance in these individuals. METHODS: Twenty-two elderly women were randomly assigned into two groups: EXE (n = 12) and CON (n = 10). Both interventions were performed twice a week for 6 weeks (12 sessions). Blood samples were obtained before intervention, after the first session, and 1 hour after the last session. Cognitive performance was evaluated before and after intervention. RESULTS: Both EXE and CON interventions ameliorated cognitive performance, improved inflammatory profile, enhanced BDNF levels, and induced histone H4 and H3 hyperacetylation status in elderly women. CONCLUSION: Our study demonstrated that the proposed interventions can be considered important strategies capable of promoting cognitive improvement in healthy elderly women. The acetylation status of histones and inflammatory cytokines are possible molecular mechanisms that mediate this beneficial response, being distinctly modulated by acute and long-term exposure.

Forced treadmill exercise prevents oxidative stress and memory deficits following chronic cerebral hypoperfusion in the rat.

Physical activity impacts functional recovery following stroke in humans, however its effects in experimental animals submitted to chronic cerebral hypoperfusion have not been investigated. The aim of this study was to evaluate the therapeutic potential of exercise, as assessed by cognitive activity in the Morris water maze and the brain oxidative status, through measurement of macromolecules damage, TBARS levels and total cellular thiols, as well as antioxidant enzymes in hippocampus, striatum and cerebral cortex. Adult male Wistar rats were submitted to the modified permanent bilateral occlusion of the common carotid arteries (2VO) method, with right common carotid artery being first occluded, and tested 3 months after the ischemic event. The effects of three different exercise protocols were examined: pre-ischemia, post-ischemia and pre+post-ischemia. Physical exercise consisted of sessions of 20-min, 3 times per week during 12 weeks (moderate intensity). Rats were submitted to cognitive assessment, in both reference and working spatial memory and after the last testing session were sacrificed to have oxidative stress parameters determined. Hypoperfusion caused a significant cognitive deficit in both spatial water maze tasks and this effect was reversed in rats receiving exercise protocol post and pre+post the ischemic event. Moreover, forced regular treadmill exercise regulated oxidative damage and antioxidant enzyme activity in the hippocampus. These results suggest that physical exercise protects against cognitive and biochemical impairments caused by chronic cerebral hypoperfusion.

Time-dependent effects of treadmill exercise on aversive memory and cyclooxygenase pathway function.

Exercise induces brain function adaptations and improves learning and memory; however the time window of exercise effects has been poorly investigated. Studies demonstrate an important role for cyclooxygenase-2 (COX-2) pathway function in the mechanisms underlying memory formation. The aim of present work was to investigate the effects of treadmill exercise on aversive memory and COX-2, PGE(2) and E-prostanoid receptors contents in the rat hippocampus at different time points after exercise has ended. Adult male Wistar rats were assigned to non-exercised (sedentary) and exercised (running daily for 20min, for 2weeks) groups. The inhibitory avoidance task was used to assess aversive memory and the COX-2, PGE(2) and E-prostanoid receptors (EP1, EP2, EP3 and EP4) levels were determined 1h, 18h, 3days or 7days after the last training session of treadmill exercise. The step down latency in the inhibitory avoidance, COX-2 and EP4 receptors levels were acutely increased by exercise, with a significant positive correlation between aversive memory performance and COX-2 levels. Increased EP2 content decreased PGE(2) levels were observed 7days after the last running session. The treadmill exercise protocol facilitates inhibitory avoidance memory and induces time-dependent changes on COX-2 pathways function (COX-2, PGE(2) and EP receptors).

Effect of landfill leachate on oxidative stress of brain structures and liver from rodents: modulation by photoelectrooxidation process.

The decomposition of solid waste in landfill is responsible for the formation of leachate, a dark liquid with an unpleasant odor; studies investigating its toxicity on mammals are rare. Oxidative stress has been considered as an important biochemical mechanism of the toxicity of several xenobiotics. The aim of this study was to evaluate the effects of landfill leachate on oxidative parameters in striatum, hippocampus and liver homogenates of mice and rats. In order to propose a clean technology for the treatment of leachate, we also investigated the effects of landfill leachate submitted to photoelectrooxidation process (PEO). The homogenates of cerebral structures and liver of Swiss albino mice and Wistar rats were incubated with different concentrations of non-PEO landfill leachate and PEO-treated landfill leachate. After the incubation, the levels of free radicals, determined by 2',7'-dichlorofluorescein diacetate probe, and the lipoperoxidation, quantified by the thiobarbituric acid reactive substances, were evaluated. There was an increase on the levels of free radicals in striatum of both mice and rats when exposed to non-PEO leachate. Moreover, PEO-treated leachate increased the lipoperoxidation in striatum homogenates from rodents. However, both leachates did not alter any of the parameters evaluated in the hippocampus. In the liver, the incubation with leachates induced an augment on levels of free radicals only in samples of mice. In addition, PEO-treated leachate increased the lipoperoxidation indexes in the liver of mice and rats. These results suggest that the landfill leachate can induce an oxidative stress state in the liver and the striatum of rodents. Additionally, the PEO process was unable to efficiently alter the toxic compounds of landfill leachate.

Correlation Between Inflammatory and Epigenetic Marks With Aerobic Performance in 10-km Runners.

Purpose: Our goals were to evaluate the effect of a 10-km running trial on inflammatory and epigenetic markers of 10-km runners and correlate the biochemical findings with anthropometric variables and performance. Methods: Twenty trained 10-km runners and seven sedentary male volunteers were recruited. Venous blood samples were collected at different times: under resting conditions, before the 10 Km race, and immediately after the finish. Inflammatory markers (IL-6, IL-10, and IL-ß) and cortisol levels were evaluated in plasma, while DNA methyltransferases (DNMT1 and DNMT3b) contents were measured in peripheral blood mononuclear cells (PBMCs). Results: Higher levels of plasma IL-6 levels were observed in 10-km runners compared to the sedentary group. After the trial, the runners had a significant increase on IL-6, IL-10, and cortisol plasma levels compared to baseline. Conclusion: Our findings suggest that inflammatory profile, but not DNMT content, influences aerobic performance in 10-km runners.

Potential Anticarcinogenic Effects From Plasma of Older Adults After Exercise Training: An Exploratory Study.

Aim: To evaluate the impact of exercise training plasma on in vitro prostate cancer cell viability and proliferation. Methods: PC3 prostate cancer cells were incubated with plasma obtained from young men with high and low physical fitness (PF) (high PF, n = 5; low PF, n = 5) and with the plasma collected from institutionalized older adults (n = 8) before and after multimodal exercise training. Cell viability and proliferation, mitochondria membrane polarization, reactive oxygen species (ROS) generation, and apoptosis were evaluated after the cell treatment with plasma. Systemic cytokines were evaluated in the plasma of institutionalized older adults submitted to an exercise training protocol. Results: Plasma from high-PF men lowers both cell viability and proliferation after the incubation time. PC3 cells also presented lower cell viability and diminished rates of cell proliferation after the incubation with post-training plasma samples of the older adults. The incubation of PC3 cells with post-training plasma of older adults depolarized the mitochondrial membrane potential and increased mitochondrial reactive oxygen species production. Post-training plasma did not change apoptosis or necrosis rates in the PC3 cell line. Multimodal exercise training increased the plasma levels of IL-2, IL-10, IFN-α, and FGF-1 and decreased TNF-α concentrations in institutionalized older adults. Conclusion: Adaptations in blood factors of institutionalized older adults may alter cell viability and proliferation by targeting mitochondrial ROS in a prostate cancer cell line.

Maternal resistance exercise promotes changes in neuroplastic and epigenetic marks of offspring's hippocampus during adult life.

Studies indicate that gestational exercise practice positively impacts the offspring's cognition. Nevertheless, the influence of maternal resistance exercise, different periods of exercise practice, and the inter- and transgenerational effects involved in these responses are not known. This study sought to report the influence of the maternal practice of resistance exercise on offspring's cognitive function, exploring behavior, and neuroplastic and epigenetic marks in the hippocampus. Female Wistar rats were divided into four groups: sedentary (SS), exercised during pregnancy (SE), exercised before pregnancy (ES), and exercised before and during pregnancy (EE). Exercised rats were submitted to a resistance exercise protocol (vertical ladder climbing). Between postnatal days (P)81 and P85, male offspring were submitted to the Morris water maze test. At P85, the following analyses were performed in offspring's hippocampus: expression of IGF-1 and BrdU+ cells, global DNA methylation, H3/H4 acetylation, and HDAC2 amount. Only the offspring of SE mothers presented subtly better performance on learning and memory tasks, associated with lower HDAC2 amount. Offspring from ES mothers presented an overexpression of hippocampal neuroplastic marks (BrdU+ and IGF-1), as well as a decrease of DNA methylation and an increase in H4 acetylation. Offspring from EE mothers (continuously exercised) did not present modifications in plasticity or epigenetic parameters. This is the first study to observe the influence of maternal resistance exercise on offspring's brains. The findings provide evidence that offspring's hippocampus plasticity is influenced by exercise performed in isolated periods (pre- or gestationally) more than that performed continually.

The impact of red grape juice (Vitis labrusca)consumption associated with physical training on oxidative stress, inflammatory and epigenetic modulation in healthy elderly women.

The imbalance of epigenetic, oxidative stress and inflammatory markers is associated with the aging physiopathology. Then, the influence of bioactive nutritional compounds and physical training on these biomarkers has been studied, although the combination of both strategies has been not investigated. Therefore, our aim was to verify the effect of the association of physical training with red grape juice (Vitis labrusca) consumption on global histone acetylation H3 and H4 levels, oxidative stress markers and interleukin 6 (IL-6) levels in peripheral blood of healthy elderly women. This double-blind randomized clinical study consisted of 29 volunteers, aged 59 years and over, divided into three groups: grape juice group (GJG, n = 9); placebo and exercise group (PLEG, n = 10) and grape juice and exercise group (GJEG, n = 10). During 1 month, GJG consumed 400 ml of grape juice per day (integral and conventional), while the PLEG and GJEG groups, besides consuming juice or placebo were submitted to a concurrent physical training protocol (two times per week, 60 min / session). The volunteers were submitted to blood collections before and after the intervention for the biomarkers analysis, e.g. IL-6, histone acetylation H3 and H4, lipid oxidative damage (TBARS), proteins (Carbonyl), non-enzymatic antioxidant defense (Sulfhydryl groups) and activity of antioxidant enzymes (superoxide dismutase and catalase). There were no statistically significant differences in the global levels of histone acetylation H3 and H4 post intervention compared to the basal period as well and between groups were found. However, PLEG and GJEG showed a remarkable reduction on IL-6 levels after intervention. We also observed an increase in Carbonyl levels, SOD activities and Sulfhydryl levels comparing before and after intervention. Considering the interaction of time and groups, a significant increase in Sulfhydryl levels only in GJG was found. The physical training protocol associated or not with grape juice consumption showed anti-inflammatory effects and an influence in the antioxidant defenses (non enzymatic and enzymatic) in elderly women. However in grape juice group, without exercise, we observed an increase in non enzymatic antioxidant defense, what could be attributed to the polyphenols content. These responses seem not to be involved with histone acetylation status.

Kinesiotherapy With Exergaming as a Potential Modulator of Epigenetic Marks and Clinical Functional Variables of Older Women: Protocol for a Mixed Methods Study.

BACKGROUND: Kinesiotherapy is an option to mitigate worsening neuropsychomotor function due to human aging. Moreover, exergames are beneficial for the practice of physical therapy by older patients. Physical exercise interventions are known to alter the epigenome, but little is known about their association with exergames. OBJECTIVE: We aim to evaluate the effects of kinesiotherapy with exergaming on older women's epigenetic marks and cognitive ability, as well as on their clinical functional variables. Our hypothesis states that this kind of therapy can elicit equal or even better outcomes than conventional therapy. METHODS: We will develop a virtual clinic exergame with 8 types of kinesiotherapy exercises. Afterward, we will conduct a 1:1 randomized clinical trial to compare the practice of kinesiotherapy with exergames (intervention group) against conventional kinesiotherapy (control group). A total of 24 older women will be enrolled for 1-hour sessions performed twice a week, for 6 weeks, totaling 12 sessions. We will assess outcomes using epigenetic blood tests, the Montreal Cognitive Assessment test, the Timed Up and Go test, muscle strength grading in a hydraulic dynamometer, and the Game Experience Questionnaire at various stages. RESULTS: The project was funded in October 2019. Game development took place in 2020. Patient recruitment and a clinical trial are planned for 2021. CONCLUSIONS: Research on this topic is likely to significantly expand the understanding of kinesiotherapy and the impact of exergames. To the best of our knowledge, this may be one of the first studies exploring epigenetic outcomes of exergaming interventions. TRIAL REGISTRATION: Brazilian Clinical Trials Registry/Registro Brasileiro de Ensaios Clínicos (ReBEC) RBR-9tdrmw; https://ensaiosclinicos.gov.br/rg/RBR-9tdrmw. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/32729.

Effects of a multimodal exercise protocol on functional outcomes, epigenetic modulation and brain-derived neurotrophic factor levels in institutionalized older adults: a quasi-experimental pilot study.

Epigenetic changes have been shown to be associated with both aging process and aging-related diseases. There is evidence regarding the benefits of physical activity on the functionality, cognition, and quality of life of institutionalized older adults, however, the molecular mechanisms involved are not elucidated. The purpose of this pilot study was to investigate the effects of a multimodal exercise intervention on functional outcomes, cognitive performance, quality of life (QOL), epigenetic markers and brain-derived neurotrophic factor (BDNF) levels among institutionalized older adult individuals. Participants (n = 8) without dementia who were aged 73.38 ± 11.28 years and predominantly female (87.5%) were included in this quasi-experimental pilot study. A multimodal exercise protocol (cardiovascular capacity, strength, balance/agility and flexibility, perception and cognition) consisted of twice weekly sessions (60 minutes each) over 8 weeks. Balance (Berg Scale), mobility (Timed Up and Go test), functional capacity (Six-Minute Walk test), cognitive function (Mini-Mental State Examination) and QOL (the World Health Organization Quality of Life-BREF Scale questionnaire) were evaluated before and after the intervention. Blood sample (15 mL) was also collected before and after intervention for analysis of biomarkers global histone H3 acetylation and brain-derived neurotrophic factor levels. Significant improvements were observed in cognitive function, balance, mobility, functional capacity and QOL after the intervention. In addition, a tendency toward an increase in global histone H3 acetylation levels was observed, while brain-derived neurotrophic factor level remained unchanged. This study provided evidence that an 8-week multimodal exercise protocol has a significant effect on ameliorating functional outcomes and QOL in institutionalized older adult individuals. In addition, it was also able to promote cognitive improvement, which seems to be partially related to histone hyperacetylation status. The Ethics Research Committee of Centro Universitário Metodista-IPA, Brazil approved the current study on June 6, 2019 (approval No. 3.376.078).

Aquatic exercise associated or not with grape juice consumption-modulated oxidative parameters in Parkinson disease patients: A randomized intervention study.

Parkinson's disease (PD) is a neurodegenerative disorder with significant motor disabilities and cognitive decline. Importantly, the imbalance of oxidative stress is related to PD physiopathology and progression. This study aimed to evaluate the impact of grape juice consumption associated with an aquatic exercise protocol on oxidative stress parameters and cognitive function in individuals with PD. The participants were randomized into two groups: grape juice group (GJG) and control group (CG) and were submitted to 4 weeks of an aquatic intervention (twice a week, approximately 60 minutes/session). The GJG also consumed 400 ml of grape juice per day (integral and conventional) during this period. Cognitive function was assessed by the Montreal Cognitive Assessment (MoCa) questionnaire. For the analysis of oxidative stress markers, specifically lipid oxidative damage (TBARS), proteins (Carbonil), acid uric and the activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase), blood collection were done before and after intervention. No changes were observed in cognitive function after intervention in both groups. Regarding biomarkers, a reduction of antioxidant enzymes, thiobarbituric acid reactive substances (TBARS) and uric acid was observed in both groups. However, only the GJG showed a significant reduction on protein oxidation levels after intervention. In conclusion, the consumption of grape juice associated with an aquatic exercise protocol might be consider an effective alternative to reduce the oxidative damage in PD, reinforcing the importance of this intervention in promoting beneficial impact in this population.

Therapeutic effectiveness of a single exercise session combined with WalkAide functional electrical stimulation in post-stroke patients: a crossover design study.

A growing body of evidence has suggested that the imbalance of epigenetic markers and oxidative stress appears to be involved in the pathophysiology and progression of stroke. Thus, strategies that modulate these biomarkers might be considered targets for neuroprotection and novel therapeutic opportunities for these patients. Physical exercise has been reported to induce changes in these epigenetic markers and improve clinical outcomes in different populations. However, little is reported on this in post-stroke patients. The purpose of this study was to investigate the effect of a single exercise session with WalkAide functional electrical stimulation (FES) on cognitive performance, clinical functional parameters, oxidative stress and epigenetic modulation in post-stroke individuals. In this crossover design study, 12 post-stroke individuals aged 54-72 years of either sexes were included and subjected to a single session of exercise (45 minutes) without WalkAide functional electrical stimulation (EXE alone group), followed by another single session of exercise (45 minutes) with WalkAide functional electrical stimulation (EXE + FES group). The clinical functional outcome measures, cognitive performance and blood collections for biomarker measurements were assessed pre- and post-intervention. After intervention, higher Berg Balance Scale scores were obtained in the EXE + FES group than in the EXE alone group. There was no significant difference in the Timed Up and Go test results post-intervention between EXE alone and EXE + FES groups. After intervention, a better cognitive performance was found in both groups compared with before the intervention. After intervention, the Timed Up and Go test scores were higher in the EXE + FES group than in the EXE alone group. In addition, the intervention induced lower levels of lipid peroxidation. After intervention, carbonyl level was lower, superoxide dismutase activity and superoxide dismutase/catalase activity ratio were higher in the EXE + FES group, compared with the EXE group alone. In each group, both histone deacetylase (HDAC2) and histone acetyltransferase activities were increased after intervention compared with before the intervention. These findings suggest that a single exercise session with WalkAide FES is more effective on balance ability and cognitive performance compared with conventional exercise alone in post-stroke patients. This is likely to be related to the regulation of oxidative stress markers. The present study was approved by the Research Ethics Committee of the Methodist University Center-IPA (approval No. 2.423.376) on December 7, 2017 and registered in the Brazilian Registry of Clinical Trials-ReBEC (RBR-9phj2q) on February 11, 2019.

Exercise-induced BDNF production by mononuclear cells of sedentary and physically active obese men.

BACKGROUND: Obesity and low physical activity changes the redox state and neurotrophin secretion by leukocytes. However, the role of exercise on brain derived neurotrophic factor (BDNF) production and oxidative stress markers of peripheral blood mononuclear cells (PBMC) remains unknown. This study aimed to verify the impact of acute maximal exercise on oxidative stress markers and the BDNF production by stimulated PBMC from sedentary and physically active obese men. METHODS: PBMC from twelve sedentary obese (SED group) and twelve regular exercisers (EXE group) obese men were collected before, immediately and 1-h after maximal exercise. PBMC were stimulated with lipopolysaccharide (LPS) to evaluate the BDNF and nitrite production, lipid peroxidation, and antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) activities. RESULTS: PBMC from EXE group presented higher BDNF production (P=0.03) and lower TBARS levels than SED group at baseline. Maximal exercise increased BDNF and nitrite production, and lipid peroxidation immediately and 1-h after the bout in both groups. The EXE group presented higher superoxide dismutase activity immediately after bout and higher catalase activity 1-h after bout in PBMC. On the other hand, PBMC from SED group had lower superoxide dismutase activity immediately after exercise. Furthermore, PBMC from EXE group presented higher BDNF production and SOD activity and lower TBARS concentrations than SED group immediately after maximal exercise. CONCLUSIONS: Maximal exercise changes the redox state and enhances BDNF production by LPS-stimulated PBMC in obese individuals.

Effect of exercise and grape juice on epigenetic modulation and functional outcomes in PD: A randomized clinical trial.

OBJECTIVE: This study aimed to investigate the impact of an aquatic physical training program associated with grape juice (Vitis labrusca) consumption on functional outcomes, Brain-Derived Neurotrophic Factor (BDNF) and global histone H4 acetylation levels in peripheral blood from individuals with Parkinson's disease. METHODS: Nineteen participants were randomized to Aquatic Exercise (AQ, n = 9) and Aquatic Exercise + Grape Juice (AQ+GJ, n = 10) groups and performed to 4 weeks of an aquatic intervention (twice a week, approximately 60 min/session). The AQ+GJ groups also consumed 400 mL of grape juice per day during this period. Functional capacity (six-min walk test, 6MWT), mobility (The Timed Up and Go, TUG) and the risk of falls (Berg Balance Scale, BBS) were evaluated before and after intervention. In addition, blood collections were carried out for biomarker analysis (e.g. BDNF and global histone H4). RESULTS: The aquatic exercise program induced functional improvement in individuals with Parkinson's disease, specifically ameliorating their mobility and functional capacity. In addition, enhanced levels of BDNF and histone H4 acetylation were found after the intervention. Grape juice consumption did not potentiate these effects, since any significant differences between the AQ and AQ+GJ groups were not found in all analysed variables. CONCLUSIONS: The present study provides important insights about aquatic exercise-modulated BDNF levels in individuals with Parkinson's disease in combination with functional improvements, suggesting that histone acetylation status may interact to dictate the molecular mechanisms involved in this response. Parkinson disease, aquatic exercise, BDNF, epigenetic, grape juice.

Immunoregulation induced by autologous serum collected after acute exercise in obese men: a randomized cross-over trial.

In this study, we evaluated the effects of autologous serum collected after two types of exercise on the in vitro inflammatory profile and T cell phenotype of resting peripheral blood mononuclear cells (PBMCs) in obese men. Serum samples and PBMCs were obtained from eight obese men who performed two exercise bouts-high intensity interval exercise (HIIE) and exhaustive exercise session to voluntary fatigue-in a randomized cross-over trial. Pre-exercise PBMCs were incubated with 50% autologous serum (collected before and after each exercise bout) for 4 h. In vitro experiments revealed that post-HIIE serum reduced the histone H4 acetylation status and NF-κB content of PBMCs and suppressed the production of both TNF-α and IL-6 by PBMCs, while increasing IL-10 production. Post-exhaustive exercise serum induced histone H4 hyperacetylation and mitochondrial depolarization in lymphocytes and increased TNF-α production. In vitro post-HIIE serum incubation resulted in an increase in the frequencies of CD4 + CTLA-4 + and CD4 + CD25+ T cells expressing CD39 and CD73. Post-exhaustive exercise serum decreased the frequency of CD4 + CD25 + CD73+ T cells but increased CD4 + CD25-CD39 + T cell frequency. Both post-exercise serums increased the proportions of CD4 + PD-1 + and CD8 + PD-1+ T cells. Blood serum factors released during exercise altered the immune response and T cell phenotype. The type of exercise impacted the immunomodulatory activity of the post-exercise serum on PBMCs.

Aquatic exercise program-modulated oxidative stress markers in patients with Parkinson's disease.

Parkinson's disease is a neurodegenerative disease. Oxidative stress, i.e., the imbalance between the generation of reactive oxygen species and the antioxidant defense capacity of the body, plays an important role in the pathogenesis of this disease. Physical exercise can regulate oxidative stress. The purpose of this study was to analyze the short- and long-term effects of an aquatic exercise program on oxidative stress levels in patients with Parkinson's disease. The aquatic exercise program was carried out during 1 month with two sessions per week (1 hour/session). Blood samples were collected at four different time points: pre-intervention, immediately, 48 hours, and 30 days after the first session of aquatic exercise program. Our results revealed that water-based programs modulated antioxidant enzyme activity, increased superoxide dismutase activity, reduced catalase activity, and increased the ratio of superoxide dismutase activity to catalase activity in patients with Parkinson's disease. Compared with pre-intervention and 48 hours after the first session of aquatic exercise program, superoxide dismutase activity was higher and catalase activity was lower immediately and 30 days after the first session. Our results demonstrated that aquatic exercise program could modulate oxidative stress, mainly by the effect of antioxidant enzyme activity. These results could better help understand the target of oxidative stress in Parkinson's disease. This study was approved by the Ethics Committee of Centro Universitário Metodista IPA (approval No. 1.373.911) on August 9, 2019 and registered with REBEC (registration number: RBR-6NJ4MK).