Resistance Training Reduces Blood Pressure: Putative Molecular Mechanisms.

Arterial hypertension is a multifactorial clinical condition characterized by higher blood pressure levels. The main treatment for controlling high blood pressure consists of drug therapy, but the scientific literature has been pointing to the efficiency of aerobic and resistance exercises acting in a therapeutic and/or preventive way to reduce and control the blood pressure levels. Resistance training is characterized by sets and repetitions on a given muscle segment that uses overload, such as machine weights, bars, and dumbbells. As it successfully affects a number of variables associated to practitioners' functional and physiological features as well as emotional and social variables, resistance training has been a crucial part of physical exercise programs. Several reports highlight the various adaptive responses it provides, with a focus on the improvement in strength, balance, and muscular endurance that enables a more active and healthy lifestyle. Resistance training programs that are acute, sub-chronic, or chronic can help people with varying ages, conditions, and pathologies reduce their arterial hypertension. However, molecular mechanisms associated with resistance training to reduce blood pressure still need to be better understood. Thus, we aimed to understand the main effects of resistance training on blood pressure as well as the associated molecular mechanisms.

MicroRNAs regulating signaling pathways in cardiac fibrosis: potential role of the exercise training.

Cardiovascular and metabolic diseases such as hypertension, type 2 diabetes, and obesity develop long-term fibrotic processes in the heart, promoting pathological cardiac remodeling, including after myocardial infarction, reparative fibrotic processes also occur. These processes are regulated by many intracellular signaling pathways that have not yet been completely elucidated, including those associated with microRNA (miRNA) expression. miRNAs are small RNA transcripts (18-25 nucleotides in length) that act as posttranscriptionally regulators of gene expression, inhibiting or degrading one or more target messenger RNAs (mRNAs), and proven to be involved in many biological processes such as cell cycle, differentiation, proliferation, migration, and apoptosis, directly affecting the pathophysiology of several diseases, including cardiac fibrosis. Exercise training can modulate the expression of miRNAs and it is known to be beneficial in various cardiovascular diseases, attenuating cardiac fibrosis processes. However, the signaling pathways modulated by the exercise associated with miRNAs in cardiac fibrosis were not fully understood. Thus, this review aims to analyze the expression of miRNAs that modulate signaling pathways in cardiac fibrosis processes that can be regulated by exercise training.

A Real-World High-Intensity Interval Training Protocol for Cardiorespiratory Fitness Improvement.

High-Intensity Interval Training (HIIT) has emerged as an interesting time-efficient approach to increase exercise adherence and improve health. However, few studies have tested the efficiency of HIIT protocols in a "real world" setting, e.g., HIIT protocols designed for outdoor spaces without specialized equipment. This study presents a "real world" training protocol, named "beep training", and compares the efficiency of a HIIT regiment versus a traditional long-duration Moderate-Intensity Continuous Training (MICT) regiment using this beep training protocol on VO2 max of overweight untrained men. Twenty-two subjects performed outdoor running with MICT (n = 11) or HIIT (n = 11). Cardiorespiratory fitness was assessed before and after training protocols using a metabolic analyzer. Both training protocols were performed 3 days a week for 8 weeks using the Beep Test results. The MICT group performed the exercise program at 60%-75% of the maximum speed of the 20 m shuttle test (Vmax) and with a progression of the distance of 3,500-5,000 m. The HIIT group performed the interval exercise with 7-10 bouts of 200 m at 85%-100% of the maximum speed of the 20 m shuttle test (Vmax), interspersed with 1 min of passive recovery. Although the HIIT group presented a significantly lower training volume than the MICT group (p < 0.05) after 8 weeks of beep training, HIIT was superior to MICT in improving VO2 max (MICT: ~4.1%; HIIT: ~7.3%; p < 0.05). The "real world" HIIT regiment based on beep training protocol is a time-efficient, low-cost, and easy-to-implement protocol for overweight untrained men.

Reactive gliosis in Alzheimer's disease: a crucial role for cognitive impairment and memory loss.

Alzheimer's disease (AD) is a neurodegenerative disorder that leads to cognitive decline and memory loss. Insulin resistance in central nervous system (CNS) is a common feature in dementia. Defective insulin signaling is associated to higher levels of inflammation and to neuronal dysfunction. A reactive gliosis, a change that occurs in glial cells due to damage in CNS, seems to be one of the most important pro-inflammatory mechanisms in AD pathology. The first response to CNS injury is the migration of macrophages and microglia to the specific site of the injury. Oligodendrocytes are also recruited to to contribute with remyelination. The last component of a reactive gliosis is astrogliosis, which is the enhancement of astrocytes expression with concomitant changes in its morphology being the main cells of the glial scar. Here, we review the mechanisms by which a reactive gliosis can induce or contribute to the development and progression of AD.

Accumulated High-intensity Interval Training Protocol: A New Approach to Study Health Markers in Wistar Rats.

High-Intensity Interval Training (HIIT) and accumulated exercises are two time-efficient programs to improve health in humans and animal models. However, to date, there are no studies on whether HIIT performed in an accumulated fashion is as effective as a traditional HIIT performed with single daily sessions in improving health markers. This paper presents the effects of a new HIIT protocol, called accumulated HIIT, on body weight gain, maximal oxygen consumption (VO2max), and cardiac hypertrophy in young Wistar rats. Sixty-day-old male Wistar rats were assigned to three groups: untrained (UN; n = 16), HIIT performed with single daily sessions (1-HIIT; n = 16), and HIIT performed with three daily sessions (3-HIIT; n = 16). Body weight and VO2max were recorded before and after the training period. The VO2max measurements were taken using a metabolic analyzer at the maximal running velocity (Vmax). The training was performed for both HIIT groups five days per week over eight weeks with the same weekly progression of the exercise intensity (85-100% Vmax). The 1-HIIT group performed single daily sessions (6 bouts of 1 min interspersed with 1 min of passive recovery). The 3-HIIT group performed three daily sessions (2 bouts of 1 min interspersed with 1 min of passive recovery with an interval of 4 h between bouts). After the last VO2max test, the rats were euthanized, and their hearts were harvested and weighed. The results showed that 3-HIIT had similar beneficial effects to 1-HIIT in preventing body weight gain, improving VO2max, and inducing cardiac hypertrophy. These findings reveal for the first time the efficacy of an accumulated HIIT protocol on the health markers of young Wistar rats. This new HIIT protocol may be more feasible than traditional HIIT protocols as exercise can be split into very short sessions throughout a day in this new approach.

Regulation of microRNAs in Alzheimer´s disease, type 2 diabetes, and aerobic exercise training.

Alzheimer's disease (AD) is the most common type of dementia. The evolution and aggregation of amyloid beta (ß) oligomers is linked to insulin resistance in AD, which is also the major characteristic of type 2 diabetes (T2D). Being physically inactive can contribute to the development of AD and/or T2D. Aerobic exercise training (AET), a type of physical exercise, can be useful in preventing or treating the negative outcomes of AD and T2D. AD, T2D and AET can regulate the expression of microRNAs (miRNAs). Here, we review some of the changes in miRNAs expression regulated by AET, AD and T2D. MiRNAs play an important role in the gene regulation of key signaling pathways in both pathologies, AD and T2D. MiRNA dysregulation is evident in AD and has been associated with several neuropathological alterations, such as the development of a reactive gliosis. Expression of miRNAs are associated with many pathophysiological mechanisms involved in T2D like insulin synthesis, insulin resistance, glucose intolerance, hyperglycemia, intracellular signaling, and lipid profile. AET regulates miRNAs levels. We identified 5 miRNAs (miR-21, miR-29a/b, miR-103, miR-107, and miR-195) that regulate gene expression and are modulated by AET on AD and T2D. The identified miRNAs are potential targets to treat the symptoms of AD and T2D. Thus, AET is a non-pharmacological tool that can be used to prevent and fight the negative outcomes in AD and T2D.

An overview of the molecular and physiological antidepressant mechanisms of physical exercise in animal models of depression.

BACKGROUND: Depression is a global disease that affects the physical and mental health of people of all ages. Non-pharmacological and unconventional methods of treatment, such as regular physical exercise, have been recommended to treat depression. METHODS: Here, we briefly review the literature about the physiological and molecular mechanisms of exercise antidepressants in depressive-like behavior in animal models of depression. RESULTS: The main hysiological and molecular mechanisms of physical exercise in depression include blood flow changes in several areas of the brain, increase in brain serotonin synthesis, increase in antioxidant enzymes, increase in serum and brain brain-derived neuro factor (BDNF) levels, decrease in cortisol levels and reduced inflammation in peripheral and brain tissues. Physical exercise also leads to increased activation of the phosphatidylinositol-3-kinase (PI3K), PGC-1α/FNDC5/Irisin pathway, BDNF concentrations (serum and cerebral), extracellular signal-regulated kinase and cAMP-response element binding protein (mainly in neurons of the hippocampus and prefrontal cortex), which together contribute to fight or inhibit the development of depression symptoms. These molecular and physiological mechanisms work in synchrony, further enhancing their effects. CONCLUSION: Physical exercise can be used as a safe and effective non-pharmacological treatment in depression.

MicroRNAs in type 2 diabetes mellitus: potential role of physical exercise.

Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disease, and its prevalence has grown worldwide. Several pathophysiological processes contribute to the development, progression and aggravating of the disease, for example, decreased insulin synthesis and secretion, insulin resistance, inflammation, and apoptosis, all these processes are regulated by various epigenetic factors, including microRNAs (miRNAs). MiRNAs are small non-coding RNAs, which are around 20 nucleotides in length and are regulators of gene expression at the post-transcriptional level, have a specific function of inhibiting or degrading a messenger RNA target. Thus, miRNAs modulate the expression of many associated genes with the pathophysiological processes in T2DM. On the other hand, miRNAs are also modulated through physical exercise (PE), which induces a change in their expression pattern during and after exercise. Some scientific evidence shows that PE modulates miRNAs beneficially and improves the signaling pathway of insulin resistance, however, little is known about the function of PE modulating miRNAs associated with the processes of insulin secretion, inflammation, and apoptosis. Thus, the objective of this review is to identify the miRNAs expression pattern in T2DM and compare it with the exercise-induced miRNAs expression pattern, identifying the signaling pathways that these miRNAs are regulating in the processes of insulin secretion, insulin resistance, inflammation, and apoptosis in T2DM, and how PE may have a potential role in modulating these signal transduction pathways, promoting benefits for patients with T2DM.

Neurological consequences of exercise during prenatal Zika virus exposure to mice pups.

PURPOSE/AIM: Zika virus (ZIKV) infection during the pregnancy period is related to microcephaly and neurobehavioral disorders at birth, while prenatal exercise is supposed to provide neuroprotection in newborns pups. The aim of this study was to investigate the neurological consequences of exercise during prenatal ZIKV exposure to mice pups. MATERIAL AND METHODS: Twelve weeks female mice were randomly assigned into three groups: Control group, intraperitoneally injected with saline (Control); untrained group, intraperitoneally injected with ZIKV (ZIKV); and trained group, intraperitoneally injected with ZIKV (ZIKV/swim). There was one familiarization week prior to the beginning of the swimming training. Dams swam for 60 min/session, 5 days/week, during 4 weeks. Mating occurred between the fifth and seventh day of the first week of the swimming training. ZIKV 106 plaque-forming units/100 µl (106 PFUs/100 µl) or an equal volume of saline was intraperitoneally injected in the pregnant mice at embryonic day 10.5. Pup's body mass and brain weight were measured at postnatal day 1 (P1). Behavioral tests were performed from P30 to P35. Thereafter, hippocampal levels of syntaxin-1, GFAP, IBA-1, and BDNF were measured. RESULTS: Exercise during prenatal ZIKV exposure prevented brain atrophy, development of depression, anxiety, and disruption of social behavior. Exercise during prenatal ZIKV exposure inhibited the overexpression of microglia (IBA-1) and astrocytes (GFAP), with reduction of BDNF levels in the hippocampi of female and male mice pups. No significant changes were seen in syntaxin-1 levels. CONCLUSION: Our findings reveal beneficial effects of exercise during pregnancy exposure to ZIKV in mice pups.

Moderate-intensity continuous training and high-intensity interval training improve cognition, and BDNF levels of middle-aged overweight men.

The prevalence of overweight and obesity is increasing worldwide, which has been associated with poor cognitive outcomes. Participating in regular physical exercise may also improve cognition, and levels of brain-derived neurotrophic factor (BDNF), but the optimal exercise prescription remains to be elucidated. The purpose of the present study is to compare the effects of moderate intensity continuous training (MICT) and high intensity interval training (HIIT) on cognition, and serum BDNF levels in middle-aged and overweight men. Twenty-five sedentary, overweight men participated in the 8-week training intervention. Subjects were randomized into MICT (n = 12) or HIIT (n = 13) and performed exercise sessions 3x/week for 8-weeks. Cognitive function, and serum BDNF levels were assessed pre- and post-intervention. Statistical analysis was carried out using the Graph Pad Prism 7.0, and the level of significance was set at 5%. Significant improvements were observed in cognitive test scores, and BDNF levels in MICT and HIIT groups (p < 0.05). There were no significant differences in cognitive function between MICT and HIIT. The present study implicates that 8 weeks of MICT or HIIT may be a very useful non-pharmacological treatment option to improve cognitive function, and BDNF levels in middle-aged overweight men.

MicroRNAs Regulating Renin-Angiotensin-Aldosterone System, Sympathetic Nervous System and Left Ventricular Hypertrophy in Systemic Arterial Hypertension.

MicroRNAs are small non-coding RNAs that regulate gene and protein expression. MicroRNAs also regulate several cellular processes such as proliferation, differentiation, cell cycle, apoptosis, among others. In this context, they play important roles in the human body and in the pathogenesis of diseases such as cancer, diabetes, obesity and hypertension. In hypertension, microRNAs act on the renin-angiotensin-aldosterone system, sympathetic nervous system and left ventricular hypertrophy, however the signaling pathways that interact in these processes and are regulated by microRNAs inducing hypertension and the worsening of the disease still need to be elucidated. Thus, the aim of this review is to analyze the pattern of expression of microRNAs in these processes and the possible associated signaling pathways.

Physical Exercise and Immune System: Perspectives on the COVID-19 pandemic.

Physical exercise training (PET) has been considered an excellent non-pharmacological strategy to prevent and treat several diseases. There are various benefits offered by PET, especially on the immune system, promoting changes in the morphology and function of cells, inducing changes in the expression pattern of pro and anti-inflammatory cytokines. However, these changes depend on the type, volume and intensity of PET and whether it is being evaluated acutely or chronically. In this context, PET can be a tool to improve the immune system and fight various infections. However, the current COVID-19 pandemic, caused by SARS-CoV-2, which produces cytokine storm, inducing inflammation in several organs, with high infection rates in both sedentary and physically active individuals, the role of PET on immune cells has not yet been elucidated. Thus, this review focused on the role of PET on immune system cells and the possible effects of PET-induced adaptive responses on SARS-CoV-2 infection and COVID-19.

The Impact of COVID-19 on the Cardiovascular System.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces coronavirus-19 disease (COVID-19), has affected many people in Brazil and worldwide. This disease predominantly affects the organs of the respiratory system, but it also damages the brain, liver, kidneys and especially the heart. In the heart, scientific evidence shows that this virus can damage the coronary arteries, generating microvascular dysfunction, favoring acute myocardial infarction. Furthermore, with the increased expression of pro-inflammatory cytokines, it can lead to myocarditis and cardiac fibrosis, inducing changes in the electrical conduction system of the heart, generating cardiac arrhythmias. All these factors mentioned are protagonists in promoting the increase in the mortality outcome. This outcome may be even higher if the individuals are elderly, or if they have other diseases such as type 2 diabetes mellitus or hypertension, because they may already have cardiomyopathy. In this context, this review focused on the impact that COVID-19 can have on the heart and cardiovascular system and the association of this impact with aging, type 2 diabetes mellitus, cardiac arrhythmias and arterial hypertension.

Physical exercise consequences on memory in obesity: A systematic review.

Obesity is associated with changes in memory. Thus, the aim of this systematic review was to investigate the physical exercise consequences on memory in obesity. A search was carried out in the PubMed, Lilacs, and Scielo databases with the following descriptors: "physical exercise," "memory," and "obesity." A total of 16 studies were analyzed in this review. Low, moderate, and high intensity exercise training showed positive effects on memory in patients with obesity (100%). The animal models of obesity used in their physical exercise protocols: treadmill (72.7%) or wheel running (27.3%). Most of the animal studies (81.8%) revealed positive effects of the physical exercise protocol on memory in obesity. Mouse was the most commonly used animal (54.5%), and a 60% high-fat diet (HFD) was the most commonly method used to induce obesity (82%). We did not identify any knockout model of obesity that was used to evaluate memory and used physical exercise as the main intervention. Thus, exercise training, independently if it is resistance or endurance training, seems to be an excellent intervention to prevent and inhibit cognitive impairment and memory loss on obese patients and animal models of obesity.

Effects of physical exercise on memory in type 2 diabetes: a brief review.

Type 2 diabetes (T2D) is a metabolic disorder that can lead to memory impairment. T2D main features are insulin resistance and hyperglycemia. Physical exercise is a non-pharmacological intervention that can regulate glycemic levels and fight insulin resistance in T2D, but whether it influences memory has been discussed. There are 2 main types of physical exercise: aerobic exercise and resistance exercise. Here, we review about the consequences of different physical exercise protocols on memory in diabetic subjects and animal models of T2D. Physical exercise, aerobic or resistance training, most of the times, is a capable agent to prevent and treat memory loss on diabetic subjects and animal models of T2D. However, whether aerobic and resistance training combined improve memory in subjects with T2D remains controversial. Regarding animal models of T2D, aerobic and resistance training have been showed to be capable to prevent and treat memory loss. Acute and chronic protocols of exercise, generally, induce positive physiological responses and adaptations in T2D, such as a better glucose control. The ideal physical exercise protocol that will produce the best benefits to diabetic subjects and to animal models of T2D has not been described yet. A variety of combination between intensity, volume, frequency, and duration of the physical exercise protocol on future studies is necessary to both diabetic subjects and animal models of T2D to determine the best protocol that will induce more benefits on memory in T2D.

Exercise-linked consequences on epilepsy.

OBJECTIVE: Epilepsy is a brain disorder that leads to seizures and neurobiological, cognitive, psychological, and social consequences. Physical inactivity can contribute to worse epilepsy pathophysiology. Here, we review how physical exercise affects epilepsy physiopathology. METHODS: An extensive literature search was performed and the mechanisms of physical exercise on epilepsy were discussed. The search was conducted in Scopus and PubMed. Articles with relevant information were included. Only studies written in English were considered. RESULTS: The regular practice of physical exercise can be beneficial for individuals with neurodegenerative diseases, such as epilepsy by decreasing the production of pro-inflammatory and stress biomarkers, increasing socialization, and reducing the incidence of epileptic seizures. Physical exercise is also capable of reducing the symptoms of depression and anxiety in epilepsy. Physical exercise can also improve cognitive function in epilepsy. The regular practice of physical exercise enhances the levels of brain-derived neuro factor (BDNF) in the hippocampi, induces neurogenesis, inhibits oxidative stress and reactive gliosis, avoids cognitive impairment, and stimulates the production of dopamine in the epileptic brain. CONCLUSION: Physical exercise is an excellent non-pharmacological tool that can be used in the treatment of epilepsy.

Molecular mechanisms of physical exercise on depression in the elderly: a systematic review.

Depressive disorders are common among the elderly. Major depressive disorder will be one of the highest healthcare costs in middle and higher income countries by 2030. It is known that physical inactivity leads to negative effects on mental health in the elderly.The purpose of this review was to explore investigate the consequences of physical exercise (aerobic and resistance exercise) on major depressive disorder among elderly, and presenting its potential biological mechanisms. This study was designed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Clinical trials or randomized clinical trials or cohort studies participated of the study design. Ten studies were evaluated and the main outcomes of each were reported. Aerobic and resistance training revealed to be effective in fighting the symptoms of depression. The most common physical exercise protocol adopted to reduce the consequences of major depressive disorder in humans was the prescription of aerobic exercise at moderate-intensity lasting 60 min per session, 3 times per week, for 24 weeks. Physical exercise enhances IGF-I and activates PGC-1α/FNDC5/Irisin pathway. Physical exercise also increases expression of BDNF and its receptor, TrkB, in the hippocampus and prefrontal cortex leading to upstream of ERK and inhibiting depressive-like behavior. Physical exercise brings mental health benefits and plays a crucial role in avoiding the development of major depressive disorder.