BDNF Modulation by microRNAs: An Update on the Experimental Evidence.

MicroRNAs can interfere with protein function by suppressing their messenger RNA translation or the synthesis of its related factors. The function of brain-derived neurotrophic factor (BDNF) is essential to the proper formation and function of the nervous system and is seen to be regulated by many microRNAs. However, understanding how microRNAs influence BDNF actions within cells requires a wider comprehension of their integrative regulatory mechanisms. Aim: In this literature review, we have synthesized the evidence of microRNA regulation on BDNF in cells and tissues, and provided an analytical discussion about direct and indirect mechanisms that appeared to be involved in BDNF regulation by microRNAs. Methods: Searches were conducted on PubMed.gov using the terms "BDNF" AND "MicroRNA" and "brain-derived neurotrophic factor" AND "MicroRNA", updated on 1 September 2023. Papers without open access were requested from the authors. One hundred and seventy-one papers were included for review and discussion. Results and Discussion: The local regulation of BDNF by microRNAs involves a complex interaction between a series of microRNAs with target proteins that can either inhibit or enhance BDNF expression, at the core of cell metabolism. Therefore, understanding this homeostatic balance provides resources for the future development of vector-delivery-based therapies for the neuroprotective effects of BDNF.

Exercise Immunology Applied to Pediatric Sport and the Importance of Monitoring Stages of Puberty and Biological Maturation.

CONTEXT: Exercise immunology is aimed at understanding how exercise sessions can affect the immune system in athletic subjects of different age groups. The objective of the current study was to discuss in which stage of biological maturation (BM) young athletes may be more vulnerable in relation to the immune system, and whether there is a BM range in which it is safer to perform sports training with strenuous exercise loads. EVIDENCE ACQUISITION: Evidence from scientific research from several scientific disciplines (eg, immunology, sport immunology, pediatrics, sports medicine, human development) was gathered to holistically examine the main particularities of exercise immunology as applied to pediatric sport. STUDY DESIGN: Narrative review. LEVEL OF EVIDENCE: Level 5. RESULTS: In pediatric patients, lymphoid tissue expands during puberty and involutes after puberty until it returns to pre-expansion values. This suggests that there is a specific period in which the immune system may be stronger, which may provide opportunities for strenuous exercise in pediatric athletes. However, the chronological period when puberty occurs will be determined by BM, which is the rate at which the biological systems of the human body improves. This may affect the period of lymphoid tissue expansion and, consequently, the behavior of the immune system in pediatric subjects of the same age category. CONCLUSION: During puberty, there is a significant increase in the proinflammatory profile; to compensate for this, there is an expansion of lymphoid tissue that may favor the efficiency of the immune system. The period in which puberty is reached may vary according to the stages of BM. Therefore, in exercise immunology applied to pediatric sports, in addition to external and internal training loads, it is necessary to consider BM and puberty, which have been shown to be safer biomarkers than chronological age for determining immune system behavior in pediatric athletes. STRENGTH-OF-RECOMMENDATION TAXONOMY (SORT): Evidence B level 3.

Exercise and Weight Management: The Role of Leptin-A Systematic Review and Update of Clinical Data from 2000-2022.

A well-balanced metabolism means a lower risk for metabolism-related neuropsychiatric disorders. Leptin is a secretory adipokine involved in the central control of appetite that appears to play a role in the etiology of feeding-related disorders. Additionally, the influence of exercise on feeding behaviors potentially modulates the circulation of metabolites that signal through the central nervous system. In this systematic review, we collected the recent clinical evidence on the effect of exercise on leptin concentrations in health individuals published from 2000 to 20 September 2022, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA 2020 statement). Six hundred and thirty-eight papers were retrieved and forty-eight papers were included in the qualitative synthesis. Data supports that exercise positively influences appetite via enhancing peripheral and central leptin signaling (reuptake), especially during weight loss. Exercise modulation of leptin signaling through leptin receptors helps to stabilize increases in food intake during periods of negative energy balance, prior to a decrease in the body fat tissue content. At a high intensity, exercise appears to counteract leptin resistance.

The Body Adiposity Index is not applicable to the Brazilian adult population.

Background: Obesity is a serious disease that burdens public health systems around the world. It is a risk factor for the development of several non-communicable chronic diseases that are related to the amount and distribution of body fat. Body composition assessment using simple and low-cost techniques can help in the early detection of excess fat, allowing for the prevention and treatment of both obesity and associated diseases. Thus, identifying and proposing valid anthropometric indices for this purpose can be a great ally of health programs. Objective: To verify the validity of the Body Adiposity Index (BAI) in relation to Dual Energy X-Ray Absorptiometry (DXA) for estimating body fat percentage in Brazilian adults, as well as to propose a new mathematical model to estimate the fat-free mass of this population. Methods: In a cross-sectional study, 424 subjects (of which 220 were women), aged between 20 and 59 years, were evaluated by BAI and DXA, then randomly divided into two groups stratified by sex: the development group (n = 283) and the cross-validation group (n = 141). Statistical analyses to test the validity of BAI as a predictor of fat mass, in addition to proposing a new mathematical model for estimating fat-free mass, using DXA as a reference method. The analysis included paired t-test, stepwise multiple regression, coefficient of concordance correlation, and Bland-Altman plots. Results: The BAI validity analysis showed a low correlation coefficient of agreement [CCC = 0.626; ρ (precision) = 0.795; Cb(accuracy) = 0.787]; in addition, the mean difference in the Bland-Altman plot was different from zero in the cross-validation group (p < 0.01) and limits of agreement (LOA) ranged between-8.0 and 14.4 kg, indicating a poor agreement between the BAI and the reference method. The new mathematical model for estimating FFM showed a high correlation coefficient of agreement (CCC = 0.952; ρ = 0.953; Cb = 0.999), in addition to acceptable LOA in the Bland-Altman plot (-6.7 and 6.7). Conclusion: In the studied sample, the BAI showed low validity for estimating body fat, while the new proposed model was found to be a good option to assess the body composition of Brazilian adults.

The BDNF Val66Met Polymorphism is a Relevant, But not Determinant, Risk Factor in the Etiology of Neuropsychiatric Disorders - Current Advances in Human Studies: A Systematic Review.

Brain-derived neurotrophic factor (BDNF) is the brain's most-produced neurotrophin during the lifespan, essentially involved in multiple mechanisms of nervous system development and function. The production/release of BDNF requires multi-stage processing that appears to be regulated at various stages in which the presence of a polymorphism "Val66Met" can exert a critical influence. Aim: To synthesize the knowledge on the BDNF Val66Met polymorphism on intracellular processing and function of BDNF. Methods: We performed a systematic review and collected all available studies on the post-translation processes of BDNF, regarding the Val66Met polymorphism. Searches were performed up to 21st March 2021. Results: Out of 129 eligible papers, 18 studies addressed or had findings relating to BDNF post-translation processes and were included in this review. Discussion: Compilation of experimental findings reveals that the Val66Met polymorphism affects BDNF function by slightly altering the processing, distribution, and regulated release of BDNF. Regarding the critical role of pro-BDNF as a pro-apoptotic factor, such alteration might represent a risk for the development of neuropsychiatric disorders.

Leptin-A Potential Bridge between Fat Metabolism and the Brain's Vulnerability to Neuropsychiatric Disorders: A Systematic Review.

BACKGROUND: Obesity and being overweight have been described as potential causes of neurological disorders. Leptin, a peptide expressed in fat tissue, importantly participates in energy homeostasis and storage and has recently been identified for its signaling receptors in neuronal circuits of the brain. AIM: To elucidate whether the endogenous modulation of leptin can be a protection against neuropsychiatric disorders. METHOD: A systematic review was performed in accordance with the PRISMA-P method, and reports of studies containing data of leptin concentrations in healthy individuals with or without obesity were retrieved from the PubMed database, using the combinations of Mesh terms for "Leptin" and "Metabolism". RESULTS: Forty-seven randomized and non-randomized controlled trials, dating from 2000 to 2021, were included in the qualitative synthesis. DISCUSSION AND CONCLUSIONS: Leptin secretion displays a stabilizing pattern that is more sensitive to a negative energy intake imbalance. Leptin levels influence body weight and fat mass as a pro-homeostasis factor. However, long-term exposure to elevated leptin levels may lead to mental/behavioral disorders related to the feeding and reward systems.

Lean mass and biological maturation as predictors of muscle power and strength performance in young athletes.

BACKGROUND: The biological maturation (BM) analyzed by peak height velocity (PHV) and bone age (BA), and lean body mass has been associated with the strength and muscle power of young athletes. However, the ability of BM (PHV and BA) and LM markers to predict muscle strength and power in young athletes remains uncertain. OBJECTIVE: The Aim was determine the predicting power of BM markers (PHV and BA) and LM in relation to muscle power of upper and lower limbs and muscle strength of upper limbs in adolescent athletes at puberty. METHODS: Ninety-two adolescent athletes (both sexes; age 12.4 ± 1.02 years) were assessed for body composition by dual-energy X-ray absorptiometry (DXA). Power of upper limbs (ULP), force handgrip (HG), vertical jump (VJ) and countermovement jump (CMJ) were recorded. BM was predicted by mathematical models to estimate PHV and BA. Multilayer artificial neural network analyses (MLP's) were used to determine the power of prediction of LM, PHV and BA on muscle power and strength of upper- and lower-limbs of the athletes. RESULTS: LM, BA and PHV were associated with HG (r>0.74, p<0.05) and ULS (r>0.60, p<0.05) in both sexes. In both sexes BA was associated with VJ (r>0.55, p<0.05) and CMJ (r>0.53, p<0.05). LM indicated associations (r>0.60, p<0.05) with BA and with PHV (r<0.83, p<0.05) in both sexes. MLP's analysis revealed that the LM provides > 72% of probability to predict the muscle power of upper- and lower-limbs, and the strength of the upper limbs; whereas PHV provides > 43% and bone age >64% in both female and male adolescent athletes. CONCLUSION: We identified that, like PHV and BA, LM is a strong predictor of low cost of both upper limbs muscle strength and upper and lower limbs power in adolescent athletes.

The Val66 and Met66 Alleles-Specific Expression of BDNF in Human Muscle and Their Metabolic Responsivity.

Brain-derived neurotrophic factor (BDNF) plays an essential role in nervous system formation and functioning, including metabolism. Present only in humans, the "Val66Met" polymorphism of the BDNF gene (BDNF) is suggested to have a negative influence on the etiology of neurological diseases. However, this polymorphism has only been addressed, at the molecular level, in nonhuman models. Knowledge about Val66- and Met66-variant differences, to date, has been achieved at the protein level using either cell culture or animal models. Thus, the purpose of our study was to analyze the impact of the Val66Met polymorphism on BDNF expression in healthy humans and compare the allele-specific responses to metabolic stress. Muscle biopsies from 13 male recreational athletes (34 ± 9 years, 1.80 ± 0.08 m, 76.4 ± 10.5 kg) were obtained before and immediately following a VO2max test. Allele-specific BDNF mRNA concentrations were quantified by droplet digital PCR (ddPCR) in heterozygous and homozygous subjects. The results indicated that BDNF expression levels were influenced by the genotype according to the presence of the polymorphism. BDNF expression from the Met66-coding alleles, in heterozygotes, was 1.3-fold lower than that from the Val66-coding alleles. Total BDNF mRNA levels in these heterozygotes remained below the whole sample's mean. A partial dominance was detected for the Val66-coding variant on the Met66-coding's. BDNF expression levels decreased by an average of 1.8-fold following the VO2max test, independent of the individual's genotype. The results of this study indicate that metabolic stress downregulates BDNF expression but not plasma BDNF concentrations. No correlation between expression level and plasma BDNF concentrations was found.

Effect of four different forms of high intensity training on BDNF response to Wingate and Graded Exercise Test.

This study examined the effects of a nine-week intervention of four different high-intensity training modalities [high-intensity functional training (HIFT), high-intensity interval training (HIIT), high-intensity power training (HIPT), and high-intensity endurance training (HIET)] on the resting concentration of brain-derived neurotropic factor (BDNF). In addition, we evaluated the BDNF responses to Graded Exercise Test (GXT) and Wingate Anaerobic Test (WAnT) in men. Thirty-five healthy individuals with body mass index 25.55 ± 2.35 kg/m2 voluntarily participated in this study and were randomly assigned into four training groups. During nine-weeks they completed three exercise sessions per week for one-hour. BDNF was analyzed before and after a GXT and WAnT in two stages: (stage 0-before training and stage 9-after nine weeks of training). At stage 0, an increase in BDNF concentration was observed in HIFT (33%; p < 0.05), HIPT (36%; p < 0.05) and HIIT (38%; p < 0.05) after GXT. Even though HIET showed an increase in BDNF (10%) this was not statistically significant (p > 0.05). At stage 9, higher BDNF levels after GXT were seen only for the HIFT (30%; p < 0.05) and HIIT (18%; p < 0.05) groups. Reduction in BDNF levels were noted after the WAnT in stage 0 for HIFT (- 47%; p < 0.01), HIPT (- 49%; p < 0.001), HIET (- 18%; p < 0.05)], with no changes in the HIIT group (- 2%). At stage 9, BDNF was also reduced after WAnT, although these changes were lower compared to stage 0. The reduced level of BDNF was noted in the HIFT (- 28%; p < 0.05), and HIPT (- 19%;p < 0.05) groups. Additionally, all groups saw an improvement in VO2max (8%; p < 0.001), while BDNF was also correlated with lactate and minute ventilation and selected WAnT parameters. Our research has shown that resting values of BDNF after nine weeks of different forms of high-intensity training (HIT) have not changed or were reduced. Resting BDNF measured at 3th (before GXT at stage 9) and 6th day after long lasting HITs (before WAnT at stage 9) did not differed (before GXT), but in comparison to the resting value before WAnT at the baseline state, was lower in three groups. It appears that BDNF levels after one bout of exercise is depended on duration time, intensity and type of test/exercise.

BDNF Val66Met Polymorphism, the Allele-Specific Analysis by qRT-PCR - a Novel Protocol.

Background: Alteration in brain-derived neurotrophic factor (BDNF) production is a marker of neuropathological conditions, which has led to the investigation of Val66Met polymorphism occurring in the human BDNF gene (BDNF). Presently, there are no reported methods available for the analysis of Val66Met impact on human BDNF functioning. Purpose: To develop a qRT-PCR protocol for the allele-specific expression evaluation of the Val66Met polymorphism in BDNF. Methods: Using RNA extracted from muscle samples of 9 healthy volunteers (32.9 ± 10.3 y) at rest and following a maximal effort aerobic capacity exercise test, a protocol was developed for the detection of Val66/Met66 allele-specific BDNF expression in Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) - relative to housekeeping genes - and validated by absolute quantification in Droplet Digital Polymerase Chain Reaction (ddPCR). Results: Differences in the relative values of BDNF mRNA were confirmed by ddPCR analysis. HPRT1 and B2M were the most stable genes expressed in muscle tissue among different metabolic conditions, while GAPDH revealed to be metabolic responsive. Conclusion: Our qRT-PCR protocol successfully determines the allele-specific detection and changes in BDNF expression regarding the Val66Met polymorphism.

Respiratory Syndrome Coronavirus Infections: Possible Mechanisms of Neurological Implications-A Systematic Review.

Within the context of the worst pandemic of the century-Covid-19-which emerged in China and has spread across the entire globe over the last 6 months, increased knowledge about viral behavior that be prognostic is crucial. Following the patterns of other coronaviruses (CoVs), particularly those infecting the respiratory tract, neurological manifestations have been reported in patients with Covid-19. Such manifestations highlight the neurovirulence of this severe acute respiratory syndrome (SARS)-CoV2. In order to collect all available information on the implications and mechanisms of infections by respiratory CoVs, a systematic review was designed following the PRISMA protocol. The following PICO strategy (patient, problem, or population; intervention; comparison, control, or comparator; outcomes) was adopted: P included healthy individuals, patients, and animal models susceptible to human-specific viruses; I included molecular, cell culture, and comparative experimental studies; C included healthy, diseased, and immunized conditions; and O represented the virulence and pathogenicity of respiratory CoVs and their effects on the central nervous system (CNS). Searches were conducted in PubMed databases from March 30 to April 1, 2020. Results indicate the involvement of the CNS in infections with various CoVs. Infection typically begins in the airway epithelia with subsequent alveolar involvement, and the virus then spreads to the CNS via neuronal contacts with the recruitment of axonal transport. Neuronal infection and regulated cell death are the main factors causing a generalized encephalitis.

BDNF and Cortisol integrative system - Plasticity vs. degeneration: Implications of the Val66Met polymorphism.

BDNF is the neurotrophin mediating pro-neuronal survival and plasticity. Cortisol (COR), in turn, is engaged in the coordination of several processes in the brain homeostasis. Stress-responsive, both factors show an integrative role through their receptor's dynamics in neurophysiology. Furthermore, the Val66Met BDNF polymorphism may play a role in this mechanism. AIM: to investigate BDNF-COR interaction in the human neurophysiology context. METHODS: We collected all papers containing BDNF and COR parameters or showing COR analyses in genotyped individuals in a PubMed search - full description available on PROSPERO - CRD42016050206. DISCUSSION: BDNF and COR perform distinct roles in the physiology of the brain whose systems are integrated by glucocorticoid receptors dynamics. The BDNF polymorphism appears to have an influence on individual COR responsivity to stress. BDNF and COR play complementary roles in the nervous system where COR is a regulator of positive/negative effects. Exercise positively regulates both factors, regardless of BDNF polymorphism.