El papel del ejercicio físico en la inducción de BDNF y sus vías de señalización en el sistema nervioso central. Aplicación neurobiológica en modelos sanos y terapéutica en la enfermedad de Alzheimer

La actividad física previene numerosas patologías y mejora muchos rasgos fisiopatológicos en diferentes enfermedades. El ejercicio ha sido asociado clásicamente con beneficios en desórdenes musculares y metabólicos. Sin embargo, los efectos del ejercicio en la función cerebral, especialidad conocida como “Neurobiología del ejercicio”, han cobrado gran importancia en los últimos años. Los efectos beneficiosos del ejercicio físico han sido establecidos en muchas enfermedades tales como la enfermedad de Alzheimer, el Parkinson, la esclerosis lateral amiotrófica, la esquizofrenia, el trastorno bipolar y los trastornos depresivos, entre otros. Estos hallazgos han llevado a utilizar el ejercicio físico como una estrategia terapéutica coadyuvante, no sólo en el campo de la investigación sino también en la práctica clínica. De acuerdo con una gran cantidad de evidencias, el ejercicio no sólo restaura las alteraciones fisiológicas de numerosas enfermedades neuropsiquiátricas sino que también mejora la función cerebral, la cognición y el estado psicológico de personas sanas a lo largo de la vida. El ejercicio físico ejerce su acción en el cerebro a través de diferentes vías moleculares y mecanismos fisiológicos. Algunas de ellas incluyen la prevención del estrés oxidativo, la liberación de endorfinas, el restablecimiento de la señalización dopaminérgica así como aquellas acciones mediadas por los factores neurotróficos, entre otros. Los factores neurotróficos son factores de crecimiento con diferentes fuentes y vías de acción. Aunque esta familia incluye numerosos factores, cabe destacar el factor de crecimiento similar a la insulina 1 (IGF-1), el factor de crecimiento vascular endotelial (VEGF), el factor neurotrófico derivado del cerebro (BDNF), el factor de crecimiento nervioso (NGF) y las neurotrofinas 3 y 4/5 (NT-3 y NT-4/5 respectivamente). Las principales acciones mediadas por estos factores incluyen la neurogénesis hipocampal, la reparación neuronal, axonogénesis, dendrogénesis y la modulación de la transmisión sináptica, lo que conduce a una mayor plasticidad cerebral. Las consecuencias funcionales de esta modulación incluyen una mejora en la potenciación a largo plazo en procesos relacionados con la memoria y el aprendizaje, así como efectos ansiolíticos y antidepresivos. De todos los factores neurotróficos estudiados, BDNF es uno de los más importantes ya que media efectos tróficos pleiotrópicos en el cerebro. Además, también es uno de los principales factores neurotróficos inducidos por ejercicio físico crónico y agudo. Se han encontrado altos niveles de BDNF en cerebros de personas entrenadas, a través de análisis post mortem y estudios in vivo utilizando sangre extraída de la yugular, así como en estudios con animales entrenados. Su inducción cerebral ocurre principalmente en el hipocampo y en el sistema límbico por lo que ha sido asociada con numerosas mejoras cognitivas y psicológicas. No existe todavía consenso sobre las condiciones adecuadas de procesamiento de la sangre para estandarizar la medida de BDNF periférico en estudios con ejercicio físico. Las muestras de suero, plasma, sangre total y plasma rico en plaquetas con diferentes condiciones de procesamiento son usadas indistintamente en la literatura. Esto lleva a encontrar inconsistencias entre los estudios. La presente Tesis Doctoral tiene como objetivo clarificar, por un lado, los efectos del ejercicio agudo y el entrenamiento en los niveles de factores neurotróficos en sangre humana, así como el protocolo metodológico adecuado para el análisis de BDNF. Otro objetivo ha sido determinar las vías de señalización moleculares implicadas en los efectos beneficiosos del entrenamiento físico en dos modelos murinos para la enfermedad de Alzheimer. Por último, nos planteamos evaluar el posible efecto sinérgico beneficioso del ejercicio físico y un mimético farmacológico de BDNF en ratas sanas. En nuestro primer modelo experimental dividimos en dos grupos a adolescentes sanos de acuerdo a sus hábitos de ejercicio físico. El grupo entrenado incluía miembros de un equipo ciclista profesional, y por tanto altamente entrenados. El grupo control incluía sedentarios con las mismas características. Comparamos los niveles sanguíneos de IGF-1 y BDNF de ambos grupos en el periodo de pre-temporada y post-competitivo. Evaluamos el posible efecto del BDNF circulante en la activación de proteína de unión al elemento de respuesta al cAMP (CREB) en células sanguíneas mononucleares. Todos los participantes fueron también evaluados a través de análisis antropométricos, hematológicos y calorimétricos. Los niveles sanguíneos de BDNF e IGF-1 se mostraron incrementados en los adolescentes deportistas comparados con los controles sedentarios cuando se analizaron durante el periodo de pretemporada, caracterizado por implicar exigencias físicas moderadas. Este incremento no afectó a la activación de CREB. Las diferencias entre ambos grupos desaparecieron cuando se compararon los niveles de factores neurotróficos en el periodo post-competición, caracterizado por unas exigencias máximas en el rendimiento físico. En nuestro segundo modelo experimental determinamos el efecto de una sesión de ejercicio agudo en los niveles sanguíneos de BDNF en adultos sanos, bajo diferentes condiciones de procesamiento de las muestras en un análisis longitudinal (basal, inmediatamente al terminar el ejercicio y a los 30 y 60 minutos de recuperación). Las muestras sanguíneas que analizamos incluyeron el suero coagulado durante 10 minutos y 24 horas; plasma con EDTA, con y sin plaquetas; y sangre total. Encontramos un incremento de los niveles de BDNF tras la sesión de ejercicio agudo en las muestras de suero coagulado durante 24 horas y las de sangre total. Estos cambios no se evidenciaron cuando analizamos las muestras de suero coagulado durante 10 minutos, plasma total y plasma sin plaquetas. La interferencia de los anticoagulantes utilizados para el plasma y la irregular activación de las plaquetas en el suero coagulado 10 minutos produce una gran variabilidad en los niveles de BDNF. También encontramos que la temperatura de procesado de las muestras y la hemoconcentración son factores relevantes a tener en cuenta en estos estudios. En nuestro tercer modelo experimental utilizamos ratones no transgénicos y doble transgénicos (2xTg) para la enfermedad de Alzheimer. Dividimos los animales en dos grupos: sedentario y ejercicio. A los 10 meses de edad, los grupos entrenados fueron sometidos a 12 semanas de una combinación de entrenamiento forzado y voluntario. Sometimos a todos los animales a diferentes tests psicológicos y físicos. También determinamos el consumo de glucosa cerebral mediante tomografía por emisión de positrones y los marcadores bioquímicos relacionados con los niveles de β-amiloide (βA) (1-42) y su modulación a través de la proteína relacionada con el receptor de lipoproteínas de baja densidad 1 (LRP1), la señalización de BDNF (niveles de tirosina quinasa B (TrkB) y la activación de CREB), daño oxidativo (malondialdehído, glutatión y carbonilación proteica), niveles de enzimas antioxidantes (superóxido dismutasa dependiente de cobre/zinc y manganeso (Cu/Zn-SOD y Mn-SOD), glutatión peroxidasa (GPx) y catalasa (CAT)), y el contenido (citocromo-C) y biogénesis mitocondrial (coactivador-1α del receptor activado de proliferación de los peroxisomas gamma, PGC-1α). El entrenamiento mejoró el comportamiento de los ratones 2xTg así como su rendimiento físico. Estas mejoras estuvieron acompañadas de una disminución del βA (1-42) hipocampal en los ratones 2xTg. El daño oxidativo cerebral y sistémico, LRP1 y BDNF hipocampal se mostraron disminuidos en los 2xTg mientras que el ejercicio no afectó. Sin embargo, el consumo de glucosa cerebral fue superior en los ratones transgénicos y la defensa antioxidante cerebral, mediada por la CAT, incrementó en los ratones 2xTg tras el entrenamiento. Nuestro cuarto modelo experimental incluyó un modelo triple transgénico (3xTg) para la enfermedad de Alzheimer y ratones no transgénicos como control. Además, dividimos a los animales en el grupo ovariectomizado y en el grupo con cirugía simulada. Tratamos a los animales con ejercicio voluntario durante 12 semanas cuando tenían 6 meses de edad (grupos ejercicio) y mantuvimos sedentarios a los grupos controles. Finalmente utilizamos ocho grupos experimentales que incluían el modelo de Alzheimer y/o el climaterio artificial y/o el tratamiento con ejercicio. Sacrificamos a los animales y analizamos diversos biomarcadores cerebrales entre los que se incluyeron los niveles de βA y tau hiperfosforilado, la vía amiloidogénica (C99/APP), los niveles de BDNF y su señalización a través de TrkB y CREB, PGC-1α y la expresión de las enzimas antioxidantes GPx, Mn-SOD and CAT. El entrenamiento físico implementado a los ratones 3xTg y la ovariectomía no afectaron a los niveles de βA ni a la fosforilación de tau cerebral. El ejercicio, sin embargo, previno parcialmente la vía amiloidogénica en todos los casos. Además, el entrenamiento incrementó los niveles de BDNF hipocampal en los 3xTg, ovariectomizados y sus controles. Encontramos un incremento en la activación de CREB en los ratones no transgénicos y 3xTg no ovariectomizados sometidos a ejercicio. Asimismo, la expresión de CAT hipocampal incrementó en los ratones 3xTg, entrenados y sedentarios, mientras que la ovariectomía los redujo. Esta disminución fue revertida mediante el ejercicio físico. Finalmente, en el quinto modelo experimental perseguimos evaluar el posible efecto sinérgico de 6 semanas de ejercicio físico y el mimético farmacológico de BDNF, 7,8-dihidroxiflavona (7,8-DHF), en ratas jóvenes sanas. Usamos cuatro grupos experimentales que incluyeron el grupo entrenado, el tratado con 7,8-DHF y el grupo sometido a la combinación de ejercicio y 7,8-DHF. Evaluamos la cognición de los animales a través del test de reconocimiento de objetos y el estado comportamental a través del test de campo abierto. El tratamiento con 7,8-dihidroxiflavona y/o ejercicio forzado no mostró un efecto sinérgico en los parámetros psicológicos analizados. El aprendizaje y la memoria no mejoraron, mientras que el comportamiento exploratorio incrementó con todos los tratamientos, aunque principalmente con el ejercicio físico. Teniendo en cuenta todos nuestros hallazgos podemos concluir que tanto el ejercicio agudo como el entrenamiento incrementan los niveles periféricos de BDNF en humanos mientras que el entrenamiento mejora los rasgos fisiopatológicos y funcionales de dos modelos diferentes de enfermedad de Alzheimer. Así, el ejercicio ejerce beneficios cerebrales a través de un amplio abanico de mecanismos fisiológicos que incluyen la modulación de BDNF.Physical activity prevents numerous disorders and improves many pathophysiological disease features. Exercise has been classically associated to muscular and metabolic benefits. However, the effects of exercise training on brain function, specialty known as “Neurobiology of exercise”, have recently received much attention. The beneficial effects of exercise have been clearly established in several pathologies such as Alzheimer´s disease, Parkinson´s disease, amyotrophic lateral sclerosis, schizophrenia, bipolar disorder and depressive disorder, among others. These findings have lead to use exercise training as a therapeutic coadjutant strategy not only in research but also in the clinical practice. According to a large amount of evidence, physical exercise not only restores the altered physiology of several neuropsychiatric diseases but also improves the brain function, cognition and psychological condition in healthy people. Exercise exerts its action on the brain through many molecular pathways and physiological mechanisms. Some of them include the prevention of oxidative damage, release of endorphins, restoration of dopamine signaling and those actions mediated by the neurotrophic factors. Neurotrophic factors are growth factors with different sources and pathways of action. Although there are several factors included in this family of proteins, we would like to highlight the insulin-like growth factor 1 (IGF-1), the vascular endothelial growth factor (VEGF), the brain-derived neurotrophic factor (BDNF), the nerve growth factor (NGF), and the neurotrophins 3 and 4/5 (NT-3 and NT-4/5 respectively). The main actions mediated by these factors include the hippocampal neurogenesis, neuron repair, axogenesis, dendrogenesis, synaptic transmission modulation, synaptogenesis, and thereby brain plasticity. The functional consequences of their modulation include long term potentiation, improvement of learning and memory, anxiolytic and antidepressant effects. BDNF is one of the most important neurotrophic factors since it mediates pleiotropic trophic effects in the brain. In addition, it is also one of the main neurotrophic factors induced by both chronic and acute exercise. High levels of BDNF have been found in brains of exercised persons, through post mortem studies and jugular blood in vivo analysis, as well as in trained animals. The brain modulation is produced mainly in the hippocampus and limbic system and thereby it has been associated with several cognitive and psychological improvements. There is yet no consensus about the adequate blood processing conditions to standardize peripheral BDNF assessment in exercise studies. Serum, plasma, whole blood, and platelets-rich plasma with several methodological processing conditions have been indistinctly used in the literature. This leads to inconsistencies in the studies. This Doctoral Thesis aims to clarify the effects of acute exercise and training in human blood levels of neurotrophic factors as well as the appropriate methodological protocol for the BDNF analysis. We also aim to determine the molecular pathways involved in the beneficial effects of exercise training in two mice models of Alzheimer´s disease. Finally, we aim to test the possible synergistic beneficial effect of exercise training and a BDNF pharmacologic mimetic on brain function in rats.In our first experimental model, healthy adolescents were divided into two groups according to their exercise habits. The trained group included members of an elite cyclist team, and thereby highly trained. The control group included sedentary matched controls. We compared the IGF-1 and BDNF blood levels of both groups in the pre-season and post-competition period. We evaluated the possible effect of the circulating BDNF on the cAMP response element-binding (CREB) activation in peripheral blood mononuclear cells. All participants were also evaluated through anthropometric, hematological and acelerometric analysis. We found that the BDNF and IGF-1 blood levels were increased in the trained adolescents compared with the sedentary controls when we analyzed it during the pre-season, characterized by a moderate physical demand. This increment did not affect to the CREB. Moreover, the differences between both groups disappeared when we compared the neurotrophic factor levels in the post-competition period, characterized by a maximum physical performance requirement. In our second experimental model we determined the effect of an acute bout of exercise on BDNF blood levels in healthy adults under different blood processing conditions in a time-course analysis (at baseline, immediately after exercise, at 30 and 60 minutes of recovery). The blood samples that we analyzed included serum coagulated 10 minutes and 24 hours; plasma with EDTA, with and without platelets; and whole blood. We found an increment in BDNF levels after the acute exercise in the serum coagulated during 24 hours and in whole blood samples. These changes were not evident when analyzed in the serum coagulated during 10 minutes, total plasma and platelet-free plasma samples. The interference of the anticoagulants used for the plasma and the irregular platelet activation in the serum coagulated during 10 minutes led to a high variability in the BDNF levels. We have also found that the processing temperature of the samples and the hemoconcentration are relevant factors to take into account in these studies. In our third experimental model we used non transgenic and double transgenic mice (2xTg) for Alzheimer´s disease. We divided the animals into two groups: sedentary and exercised. At 10 months of age, trained groups were subjected to 12 weeks of a training combination of forced and voluntary exercise. Different psychological and physical tests were performed to the animals. We also evaluated brain glucose uptake by positron emission tomography and biochemical markers related to amyloid-β (Aβ) (1-42) levels and its modulation through the low density lipoprotein receptor-related protein 1 (LRP1), BDNF pathway (tyrosine kinase type B (TrkB) levels and CREB levels and activation), oxidative damage (malondialdehyde, glutathione, protein carbonylation), antioxidant defense levels (superoxide dismutase dependent of copper/zinc and manganese (Cu/Zn-SOD and Mn-SOD), glutathione peroxidase (GPx) and catalase (CAT)), and mitochondrial content (cytochrome-C) and biogenesis (peroxisome proliferator-activated receptor-gamma coactivator 1α, PGC-1α). The exercise training improved the behavior of the 2xTg mice as well as their physical performance. These improvements were accompanied by a hippocampal Aβ (1-42) reduction in the 2xTg mice. The cerebral and systemic oxidative damage, LRP1 and hippocampal BDNF levels were reduced in the 2xTg mice and the exercise did not affect it. Nevertheless, the brain glucose uptake was higher in the transgenic mice and the antioxidant defense, determined by the CAT, increased in the 2xTg mice after exercise. Our forth experimental model included a triple transgenic mouse model (3xTg) of Alzheimer´s disease and non transgenic mice as control. We studied the protective effect of exercise in ovariectomized mice. The exercise protocol included 12 weeks of spontaneous wheel-running. The animals were divided into eight experimental groups which included an Alzheimer´s disease model and/or artificial climacteric and/or exercise treatment. We sacrificed animals and analyzed several brain biomarkers which included the Aβ and hiperphosphorylated tau levels, the amyloidogenic pathway (C99/APP), BDNF levels and its pathway through TrkB and CREB, PGC-1α, and the expression the antioxidant enzymes GPx, Mn-SOD and CAT. The exercise training performed by the 3xTg mice and the ovariectomy did not affect to the brain Aβ and the tau hyperphosphorylated levels. Nevertheless, the exercise partially prevented activation of the amyloidogenic pathway in all cases. In addition, training incremented the hippocampal BDNF levels of the 3xTg, ovariectomized and sham. We obtained a CREB activation increment in the non transgenic and 3xTg non ovariectomized mice subjected to exercise. Moreover, the hippocampal expression of CAT increased in the 3xTg mice, trained and sedentary, whereas the ovariectomy reduced it. This was reverted through physical exercise. Finally, in the fifth experimental model we aimed to evaluate the possible synergic effects of 6 weeks of exercise training and a pharmacological BDNF mimetic, 7,8-dihydroxyflavone (7,8-DHF), in healthy young rats. Thus, we used four experimental groups which included the trained group, the group with 7,8-DHF, the group subjected to a combination of exercise and 7,8-DHF and a control group. We evaluated the cognition of the animals thought the object recognition test and their behavioral condition by the open field test. The treatment with 7,8-DHF and/or forced exercise training did not show a synergic effect on the psychological parameters analyzed. The learning and memory did not improve, whereas the exploratory behavior incremented with all treatments but especially with the exercise training. Taking together our findings we can conclude that acute and chronic exercise increases BDNF peripheral levels in humans whereas exercise training improves the pathophysiological and functional features of Alzheimer´s disease in two different transgenic models. Exercise seems to contribute to brain benefits by a wide range of physiological mechanisms including the BDNF pathway

Caffeine and Cognitive Functions in Sports: A Systematic Review and Meta-Analysis

Cognitive functions are essential in any form of exercise. Recently, interest has mounted in addressing the relationship between caffeine intake and cognitive performance during sports practice. This review examines this relationship through a structured search of the databases Medline/ PubMed and Web of Science for relevant articles published in English from August 1999 to March 2020. The study followed PRISMA guidelines. Inclusion criteria were defined according to the PICOS model. The identified records reported on randomized cross-over studies in which caffeine intake (as drinks, capsules, energy bars, or gum) was compared to an identical placebo situation. There were no filters on participants’ training level, gender, or age. For the systematic review, 13 studies examining the impacts of caffeine on objective measures of cognitive performance or selfreported cognitive performance were selected. Five of these studies were also subjected to metaanalysis. After pooling data in the meta-analysis, the significant impacts of caffeine only emerged on attention, accuracy, and speed. The results of the 13 studies, nevertheless, suggest that the intake of a low/moderate dose of caffeine before and/or during exercise can improve self-reported energy, mood, and cognitive functions, such as attention; it may also improve simple reaction time, choice reaction time, memory, or fatigue, however, this may depend on the research protocols

Caffeinated drinks and physical performance in sport: a systematic review

settings Open AccessSystematic Review Caffeinated Drinks and Physical Performance in Sport: A Systematic Review by Sergio L. Jiménez 1,*ORCID,Javier Díaz-Lara 2ORCID,Helios Pareja-Galeano 3ORCID andJuan Del Coso 1,*ORCID 1 Centre for Sport Studies, Universidad Rey Juan Carlos, Fuenlabrada, 28943 Madrid, Spain 2 Department of Nutrition, Food Science and Physiology, Faculty of Pharmacy and Nutrition, Universidad de Navarra, 31009 Pamplona, Spain 3 Department of Physical Education, Sport and Human Movement, Autonomous University of Madrid, 28049 Madrid, Spain * Authors to whom correspondence should be addressed. Academic Editor: Marilyn Cornelis Nutrients 2021, 13(9), 2944; https://doi.org/10.3390/nu13092944 Received: 8 July 2021 / Revised: 21 August 2021 / Accepted: 23 August 2021 / Published: 25 August 2021 (This article belongs to the Special Issue Effect of Energy Drinks on Physical Performance) Download PDF Browse Figures Citation Export Abstract Caffeine (1,3,7-trimethylxanthine) is one of the most common substances used by athletes to enhance their performance during competition. Evidence suggests that the performance-enhancing properties of caffeine can be obtained by employing several forms of administration, namely, capsules/tablets, caffeinated drinks (energy drinks and sports drinks), beverages (coffee), and chewing gum. However, caffeinated drinks have become the main form of caffeine administration in sport due to the wide presence of these products in the market. The objective of this systematic review is to evaluate the different effects of caffeinated drinks on physical performance in various sports categories such as endurance, power-based sports, team sports, and skill-based sports. A systematic review of published studies was performed on scientific databases for studies published from 2000 to 2020. All studies included had blinded and cross-over experimental designs, in which the ingestion of a caffeinated drink was compared to a placebo/control trial. The total number of studies included in this review was 37. The analysis of the included studies revealed that both sports drinks with caffeine and energy drinks were effective in increasing several aspects of sports performance when the amount of drink provides at least 3 mg of caffeine per kg of body mass. Due to their composition, caffeinated sports drinks seem to be more beneficial to consume during long-duration exercise, when the drinks are used for both rehydration and caffeine supplementation. Energy drinks may be more appropriate for providing caffeine before exercise. Lastly, the magnitude of the ergogenic benefits obtained with caffeinated drinks seems similar in women and men athletes. Overall, the current systematic review provides evidence of the efficacy of caffeinated drinks as a valid form for caffeine supplementation in spor

Genetic variations associated with non- contact muscle injuries in sport: A systematic review

Introduction Non-contact muscle injuries (NCMI) account for a large proportion of sport injuries, affecting athletes’ performance and career, team results and financial aspects. Recently, genetic factors have been attributed a role in the susceptibility of an athlete to sustain NCMI. However, data in this field are only just starting to emerge. Objectives To review available knowledge of genetic variations associated with sport-related NCMI. Methods The databases Pubmed, Scopus, and Web of Science were searched for relevant articles published until February 2021. The records selected for review were original articles published in peer-reviewed journals describing studies that have examined NCMI-related genetic variations in adult subjects (17–60 years) practicing any sport. The data extracted from the studies identified were as follows: general information, and data on genetic polymorphisms and NCMI risk, incidence and recovery time and/or severity. Results Seventeen studies examining 47 genes and 59 polymorphisms were finally included. 29 polymorphisms affecting 25 genes were found significantly associated with NCMI risk, incidence, recovery time, and/or severity. These genes pertain to three functional categories: (i) muscle fiber structural/contractile properties, (ii) muscle repair and regeneration, or (iii) muscle fiber external matrix composition and maintenance. Conclusion Our review confirmed the important role of genetics in NCMI. Some gene variants have practical implications such as differences of several weeks in recovery time detected between genotypes. Knowledge in this field is still in its early stages. Future studies need to examine a wider diversity of sports and standardize their methods and outcome measure

Foot Anatomical Structural Variations Increase the Risk of Falls in Older Adults

Falls are common among older adults. The purpose of this study was to demonstrate the relationship between foot anatomical structural variations and balance in older adults and quantify foot posture and stabilometry as predictors of fall risk. This case-control study of older adults classified cases or controls according to falls in the last five years. All subjects were healthy women and men > 65 years old (n = 164), who were divided into two groups: 83 individuals who had suffered from a fall in the previous five years (case group) and 81 individuals who had not suffered from a fall (control group). Hallux abductus valgus (HAV) and tailor’s bunion are stability-determining factors. Women have a higher probability of falling. HAV (p = 0.042) and tailor’s bunion (p = 0.069) also increased the fall probability. Morphological foot variations (HAV and tailor’s bunion) linked to gender and age increase fall risk among older adults. In women fallers with HAV, there was a higher possibility of falling (63.9%). According to age, in older adults with HAV, the percentage of falls is high (62%). Fallers with tailor’s bunion (60.7%) are more numerous than fallers without this pathology. Older adults with HAV and tailor´s bunion had twice the probability of suffering a fall than older people without foot anatomical structural. Foot morphology is decisive in falling risk

Optimizing Field Body Fat Percentage Assessment in Professional Soccer Players

Body composition is a determinant of performance in soccer. To estimate the body fat percentage (%BF), dual energy X-ray absorptiometry (DXA) is effective though this method is expensive and not readily accessible. This study examines the validity of widely used field methods based on anthropometric data and bioelectrical impedance analysis (BIA). Participants were 21 male Spanish First Division soccer players aged between 22 and 35 years. In each participant, body fat mass was determined by BIA and using 18 anthropometric equations including skinfold (SKF) measurements. DXA was used as reference. Correlation with DXA measurements was excellent for all equations and separate SKF measurements yet only moderate for BIA. However, only the equation recently developed for use in soccer players based on iliac crest and triceps SKFs showed no significant or standardized differences with DXA-derived %BF and these measurements also had the lowest bias. Our findings suggest that when DXA is not available, the best field method for %BF assessment in footballers is the equation based on iliac crest and triceps SKF. As another good option, we propose the sum of triceps, subscapular, supraspinal, and abdominal SKFs, as this combination also showed good correlation with DXA

Circulating microRNAs fluctuations in exercise-induced cardiac remodeling: A systematic review

MicroRNAs (miRNAs) are small non-coding RNAs that participate in gene expression regulation. It has been observed that circulating levels of miRNAs may fluctuate during exercise, showing numerous cardiac biological and physiological effects such as structural and functional adaptations. We aimed to provide an overview of the currently available information concerning the role of circulating miRNAs in cardiovascular adaptations in response to acute and/or chronic exercise training. Relevant studies published were searched in three databases: PubMed, Web of Science and Scopus. A combination of the following keywords was used: (“microRNA” OR “miRNA” OR “miR” AND “exercise” OR “training” OR “physical activity”) AND “(heart hypertrophy” OR “cardiac remodeling” OR “cardiac muscle mass” OR “cardiac hypertrophy”). Only experimental studies, written in English and conducted in healthy individuals were included. Five articles met the inclusion criteria and were finally included in this systematic review after reviewing both title, abstract and full-text. A total of thirty-six circulating cardiac-related miRNAs were analyzed, but only five of them (miR-1, miR-133a, miR-146a, miR-206 and miR-221) were directly associated with cardiac adaptations parameters, while two of them (miR-1 and miR-133a) were related to cardiac hypertrophy. Most of them were upregulated immediately after a marathon and returned to basal levels at longer times. Therefore, we conclude that, although evidence is still limited, and long-term studies are needed to obtain more robust evidence, exercise is more likely to affect circulating cardiac-related miRNAs level

Antioxidant vitamin supplementation on muscle adaptations to resistance training: A double-blind, randomized controlled trial.

Objectives The aim of this study was to examine whether antioxidant vitamin supplementation with vitamin C (VitC) and vitamin E (VitE) affects the hypertrophic and functional adaptations to resistance training in trained men. Methods This was a double-blind, randomized controlled trial in which participants were supplemented daily with VitC and VitE ( n = 12) or placebo ( n = 11) while completing a 10-wk resistance training program accompanied by a dietary intervention (300 kcal surplus and adequate protein intake) designed to optimize hypertrophy. Body composition (dual-energy x-ray absorptiometry), handgrip strength, and one-repetition maximum (1-RM), maximal force (F0), velocity (V0), and power (Pmax) were measured in bench press (BP) and squat (SQ) tests conducted before and after the intervention. To detect between-group differences, multiple-mixed analysis of variance, standardized differences, and qualitative differences were estimated. Relative changes within each group were assessed using a paired Student's t test. Results In both groups, similar improvements were produced in BP 1-RM , SQ 1-RM SQ, and BP F0 (P < 0.05) after the resistance training program. A small effect size was observed for BP 1-RM (d = 0.53), BP F0 (d = 0.48), and SQ 1-RM (d = –0.39), but not for SQ F0 (d = 0.03). Dominant handgrip strength was significantly increased only in the placebo group (P < 0.05). According to body composition data, a significant increase was produced in upper body fat-free mass soft tissue (FFMST; P < 0.05) in the placebo group, whereas neither total nor segmental FFMST was increased in the vitamin group. Small intervention effect sizes were observed for upper body FFSMT (d = 0.32), non-dominant and dominant leg FFMST (d = –0.39; d = –0.42). Although a significant increase in total body fat was observed in both groups (P < 0.05) only the placebo group showed an increase in visceral adipose tissue (P < 0.05), showing a substantial intervention effect (d = 0.85). Conclusions The data indicated that, although VitC/VitE supplementation seemed to blunt upper body strength and hypertrophy adaptations to resistance training, it could also mitigate gains in visceral adipose tissue elicited by an energy surplus.pre-print1,83 M

Physical exercise neuroprotects ovariectomized 3xTg-AD mice through BDNF mechanisms

Postmenopausal women may be more vulnerable to cognitive loss and Alzheimer's disease (AD) than premenopausal women because of their deficiency in estrogens, in addition to their usually older age. Aerobic physical exercise has been proposed as a therapeutic approach for maintaining health and well-being in postmenopausal women, and for improving brain health and plasticity in populations at high risk for AD. To study the neuroprotective mechanisms of physical exercise in a postmenopausal animal model, we submitted previously ovariectomized, six-month old non-transgenic and 3xTg-AD mice to three months of voluntary exercise in a running wheel. At nine months of age, we observed lower grip strength and some exacerbation of the behavioral and psychological symptoms of dementia (BPSD)-like involving active exploratory activities. A similar major cognitive impairment was observed of ovariectomized 3xTg-AD mice in comparison with sham-operated 3xTg-AD mice. A reduction of bodily fitness and lack of retention of memory were observed in the ovariectomized non-transgenic mice. Physical exercise protected against all deleterious behaviors and normalized learning and memory. It also protected against body frailty, as expected. Analyses of hippocampal key markers of antioxidant and neuroplasticity signaling pathways, showed that ovariectomy impairs the activation of CREB through physical exercise. Furthermore, molecular and behavioral correlates suggested a central role of BDNF in the neuroprotection mediated by physical exercise therapy against apathy and memory loss induced by ovariectomy and the AD-genotype. © 2014 Elsevier Ltd.This study was supported by grants: SAF2009-13093-C02-02, SAF2010-19498, SAF2012-39852-C02-02 and CSD2010-00045 from the Spanish MINECO; 2009/SGR/214 from the Generalitat and 062931 from the Fundació La Marató de TV3, of Catalonia; and 35NEURO GentxGent. Yoelvis García-Mesa acknowledges support received from the Fundació La Marató de TV3Peer Reviewe

Effects of Acute Vitamin C plus Vitamin E Supplementation on Exercise-Induced Muscle Damage in Runners: A Double-Blind Randomized Controlled Trial

Considering the existing controversy over the possible role of acute antioxidant vitamins in reducing exercise-induced muscle damage (EIMD), this doubled-blind, randomized and controlled trial aimed to determine whether supplementation with vitamins C and E could mitigate the EIMD in endurance-trained runners (n = 18). The exercise protocol involved a warm-up followed by 6 to 8 bouts of 1 km running at 75% maximum heart rate (HRmax). Two hours before the exercise protocol, participants took the supplementation with vitamins or placebo, and immediately afterwards, blood lactate, rate of perceived exertion and performance were assessed. At 24 h post-exercise, CK, delayed onset muscle soreness and performance were determined (countermovement jump, squat jump and stiffness test). The elastic index and vertical stiffness were calculated using a stiffness test. Immediately after the exercise protocol, all participants showed improved maximum countermovement jump, which only persisted after 24 h in the vitamin group (p 0.05). Vitamin C and E supplementation does not seem to help with EIMD in endurance-trained individual