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).

Pulmonary rehabilitation and BDNF levels in patients with chronic obstructive pulmonary disease: A pilot study.

BACKGROUND: COPD physiopathology involves multiple pathways and evidence indicates that brain-derived neurotrophic factor (BDNF) is an important biomarker associated with parameters of COPD severity. This study aimed to analyze the time course of the effects of a pulmonary rehabilitation program (PRP) on BDNF levels and on functional status in COPD patients. METHODS: Patients were enrolled in a 24-session PRP. Exercise capacity, dyspnea, health-related quality of life, and the BODE index were assessed at baseline and after the PRP. BDNF plasma levels were measured at baseline (immediately before the 1st session), after the 1st session, and before and after the 24th session. RESULTS: Sixteen patients were included. A reduction in BDNF levels was observed after the 1st session and an increase was observed between the end of the 1st session and the beginning of the 24th session. The PRP promoted an improvement in exercise capacity and health-related quality of life and a reduction in dyspnea and the BODE index. CONCLUSION: Exercise acutely reduced BDNF levels, an effect that was nullified by the overall intervention.

Does a single bout of exercise impacts BDNF, oxidative stress and epigenetic markers in spinal cord injury patients?

Our aim was to evaluate the impact of a single bout of exercise, consisting of a gait training session with body weight support (BWS), on histone acetylation status (global histone H4 and H3 acetylation levels), brain-derived neurotrophic factor (BDNF) levels, and oxidative stress markers in peripheral blood of individuals with chronic spinal cord injury (SCI). We also set out to compare these responses with those recorded after gait training performed using a walker and with no BWS. The subjects (nearly all with an incomplete spinal cord lesion) were each submitted to two 60-minute experimental sessions on separate days with a 1- week wash-out period between the interventions. The order of the sessions was randomized. Blood samples were collected before and after each experimental trial for measurement of biomarkers. The histone acetylation status and BDNF levels remained unchanged after both interventions. After the treadmill training, the participants showed a strong increase in levels of oxidative stress markers [plasma advanced oxidation protein products (AOPPs), nitrite and thiobarbituric acid-reactive substances] without changes in antioxidant mediators. Instead, elevations in AOPP and nitrite concentrations, in addition to increased levels of glutathione and catalase activity, were found after the walker training. A single bout of gait training, be it conducted on a treadmill with BWS or using a walker without BWS, is not able to alter BDNF levels and histone acetylation status in SCI patients. However, these trials can modulate oxidative stress parameters, seemingly in a protocol-dependent manner.

Glial fibrillary acidic protein levels are associated with global histone H4 acetylation after spinal cord injury in rats.

Emerging evidence has suggested global histone H4 acetylation status plays an important role in neural plasticity. For instance, the imbalance of this epigenetic marker has been hypothesized as a key factor for the development and progression of several neurological diseases. Likewise, astrocytic reactivity - a well-known process that markedly influences the tissue remodeling after a central nervous system injury - is crucial for tissue remodeling after spinal cord injury (SCI). However, the linkage between the above-mentioned mechanisms after SCI remains poorly understood. We sought to investigate the relation between both glial fibrillary acidic protein (GFAP) and S100 calcium-binding protein B (S100B) (astrocytic reactivity classical markers) and global histone H4 acetylation levels. Sixty-one male Wistar rats (aged ~3 months) were divided into the following groups: sham; 6 hours post-SCI; 24 hours post-SCI; 48 hours post-SCI; 72 hours post-SCI; and 7 days post-SCI. The results suggested that GFAP, but not S100B was associated with global histone H4 acetylation levels. Moreover, global histone H4 acetylation levels exhibited a complex pattern after SCI, encompassing at least three clearly defined phases (first phase: no changes in the 6, 24 and 48 hours post-SCI groups; second phase: increased levels in the 72 hours post-SCI group; and a third phase: return to levels similar to control in the 7 days post-SCI group). Overall, these findings suggest global H4 acetylation levels exhibit distinct patterns of expression during the first week post-SCI, which may be associated with GFAP levels in the perilesional tissue. Current data encourage studies using H4 acetylation as a possible biomarker for tissue remodeling after spinal cord injury.

Cytokine modulation in response to acute and chronic aquatic therapy intervention in Parkinson disease individuals: A pilot study.

The study aimed to compare the basal plasma levels of inflammatory markers (MCP-1, IL-1ra and IL-1ß) in Parkinson Disease group (PDG) with control healthy subjects (control group, CG), as well to investigate the acute and chronic effects of an aquatic physiotherapy program on these biomarkers in PDG. Firstly, a rest blood sampling was taken from antecubital vein of the PD and CG. After, the PD individuals were submitted to a supervisioned aquatic physiotherapy program during 1 month, twice a week (60 min/session). In order to evaluate the acute and chronic effects of the intervention on the biomarkers, blood samples were in 4 times: before the exercise program (pre), immediately after the first session, 48 h after the exercise session and 1 month after the intervention. It was observed higher levels of the pro-inflammatory cytokines IL-1ß and MCP-1 and reduced levels IL-1ra in PDG compared to the CG. Regarding the intervention effects in PDG, a remarkable reduction on IL-1ß and MCP-1 levels at 48 h when compared to the basal were found. Furthermore, after 1 month, it was observed diminished levels of MCP-1 in combination to an increase on IL-1ra. Our data support the idea that an inflammatory status is linked to PD and that MCP-1 and IL-1ra could be taken as promising biomarkers in this condition. We also demonstrated that an aquatic physiotherapy program may offer a potential intervention able to attenuate immune responses in PD individuals in a short and long-term perspective.

Endothelial function and lipid profile of individuals with schizophrenia participating in a supported employment program.

BACKGROUND: The social function of individuals with schizophrenia is usually poor and this population exhibits a sedentary lifestyle. Social participation, inclusion in the world of work in particular, might favorably interfere with the lives of these individuals by reducing sedentarism and improving their state of health. OBJECTIVE: To analyze the lipid profile and endothelial function markers among individuals with schizophrenia enrolled in a supported employment program. METHODS: Quantitative quasi-experimental study conducted with 14 individuals with schizophrenia enrolled in a labor inclusion program. Participants were assessed before enrolment (time-point 1) and one year later (time-point 2). Total cholesterol and fractions, triglycerides, serum nitrates and nitrites (endothelial function markers) were measured. The data were analyzed with software SPSS 20. RESULTS: The high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels exhibited significant changes one year after inclusion in the labor market. HDL increased from 82.30 to 98.60 mg/dL (p<0.01) and LDL decreased from 54.50 to 44.45 mg/dL (p<0.02). The triglyceride and total cholesterol levels remained stable. The nitrate and nitrite level exhibited significant reduction from 15.20 to 14.48 µMol (p<0.01). CONCLUSION: Participation in the supported employment program might have favorably influenced the participants' lipid profile and endothelial function. Nitrites have been described as mediators in the neural inflammatory process, and reduction of their levels is associated with better prognosis of chronic diseases such as schizophrenia.

INTRODUÇÃO: Pessoas com esquizofrenia habitualmente têm um funcionamento social empobrecido e são sedentárias. A participação social, especialmente a inclusão no universo do trabalho, pode interferir positivamente na vida dessas pessoas, reduzindo o sedentarismo e melhorando sua saúde. OBJETIVO: Avaliar o perfil lipídico e os marcadores da função endotelial de pessoas com esquizofrenia participantes de um programa de emprego apoiado. MÉTODO: Pesquisa quantitativa do tipo quase-experimental que avaliou um grupo de 14 sujeitos com esquizofrenia participantes de um programa de inclusão laboral. Os sujeitos foram avaliados antes de ingressarem no programa (momento 1) e um ano depois (momento 2). Foram dosados: colesterol total e frações, triglicerídeos, nitritos e nitratos séricos (marcadores da função endotelial). Os dados foram analisados com o auxílio do software SPSS 20. RESULTADOS: As frações de colesterol high density lipoprotein (HDL-C) e low density lipoprotein (LDL-C) sofreram modificações significativas após o período de um ano de inserção no mercado de trabalho. O HDL aumentou de 82,30 para 98,60 mg/dL (p<0,01). Já o LDL apresentou uma redução de 54,50 para 44,45 mg/dL (p<0,02). Os triglicerídeos e o colesterol total mantiveram-se estáveis. Com relação aos nitritos e nitratos, houve diminuição significativa de 15,20 para 14,48 µmol (p<0,01). DISCUSSÃO: A participação no programa de emprego apoiado pode ter influenciado positivamente no perfil lipídico dos sujeitos e em sua função endotelial. Além disso, os nitritos também têm sido apontados como mediadores do processo inflamatório neural e sua diminuição está associada à melhora no prognóstico de doenças crônicas como a esquizofrenia.

Maternal consumption of high-fat diet and grape juice modulates global histone H4 acetylation levels in offspring hippocampus: A preliminary study.

This study aimed to investigate the impact of maternal consumption of a hyperlipid diet and grape juice on global histone H4 acetylation levels in the offsprinǵs hippocampus at different stages of development. During pregnancy and lactation of offspring, dams were divided into 4 groups: control diet (CD), high-fat diet (HFD), control diet and purple grape juice (PGJCD) and purple grape juice and high-fat diet (PGJHFD). Male Wistar rats were euthanized at 21days of age (PN21, adolescents) and at 50days of age (PN50, adults). The maternal consumption of grape juice increased global histone H4 acetylation levels in hippocampus of adolescents pups (PN21), an indicative of enhanced transcriptional activity and increased gene expression. On the other hand, the maternal high-fat diet diminished significantly this epigenetic marker in the adult phase (PN50), suggesting gene silencing. These preliminary findings demonstrated that the maternal choices are able to induce changes on histone H4 acetylation status in hippocampus of the offspring, which may modulate the expression of specific genes. Interestingly, this response occurs in an age and stimuli-dependent manner and strongly reinforce the importance of maternal choices during gestation.

Exercise-modulated epigenetic markers and inflammatory response in COPD individuals: A pilot study.

The study investigated the effects of exercise on epigenetic signals and systemic cytokine levels in chronic obstructive pulmonary disease (COPD) individuals. Ten participants of a pulmonary rehabilitation program were submitted to 24 sessions of a supervisioned exercise protocol thrice-weekly (90min/session). Blood samples were collected at baseline, after the 1st session, before and after the 24th session. A DNA hypomethylation status was observed after the 1st session when compared at baseline, while global histone H4 acetylation status was unaltered in any time-points evaluated. No significant changes were observed on cytokine levels after the 1st session. A significant enhancement on interleukin 6 (IL-6) and a decrease on transforming growth factor-beta (TGF-ß) levels were found after the 24th session when compared to the pre 24th session. Moreover, 23 sessions of exercise were able to diminish significantly the basal levels of IL-6 and interleukin 8 (IL-8). These data suggest a potential role of epigenetic machinery in mediating the anti-inflammatory effects of exercise in COPD patients.

The modulation of inflammatory parameters, Brain-derived neurotrophic factor levels and global histone H4 acetylation status in peripheral blood of patients with Gaucher disease type 1.

OBJECTIVES: Gaucher's disease type 1 (GD1) pathophysiology includes an imbalance on brain-derived neurotrophic factor (BDNF) levels and in the inflammatory system. However, the pathways involved remain poorly understood. The hypothesis of this study is that epigenetic mechanisms might be involved, at least partially, in this phenomenon. DESIGN AND METHODS: This study investigated the BDNF modulation, global histone H4 acetylation and pro- and anti-inflammatory cytokines levels in the peripheral blood of GD1 patients (n=10) when compared with control samples (CS) (n=11). RESULTS: The results showed a significant increase in Chitotriosidase (CT) (p=0.019) and decreased ß-glucosidase (GBA) activities (p=0.001) in GD1 samples when compared to CS, for GD1 diagnostic confirmation. Reduced levels of BDNF (p=0.004) and elevated levels of TNF-α (p=0.017) and IL-4 (p=0.035) were also found in the GD group. No significant differences were observed in IL-6 or IL-17a levels between groups (p>0.05). Finally, a trend on higher global histone H4 acetylation levels (p=0.054) was observed in the control group when compared to GD1 individuals. CONCLUSIONS: Combined, these results suggest inflammatory cytokines imbalance, reduced BDNF levels and global histone H4 hypoacetylation status in GD type 1 physiopathology. These preliminary findings may open new avenues to introduce therapies and strategies in the preventive management and treatment of this population.

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.