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1.
Prog Neurobiol ; 242: 102684, 2024 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-39481590

RESUMO

Angelman syndrome (AS) is a severe neurodevelopmental disorder characterized by motor disfunction, seizures, intellectual disability, speech deficits, and autism-like behavior, showing high comorbidity with Autism Spectrum Disorders (ASD). It is known that stimulation of the serotonin receptor 7 (5-HT7R) can rescue some of the behavioral and neuroplasticity dysfunctions in animal models of Fragile X and Rett syndrome, two pathologies associated with ASD. In view of these observations, we hypothesised that alterations of 5-HT7R signalling might also be involved in AS. To test this hypothesis, we stimulated 5-HT7R with the selective agonist LP-211 to investigate its possible beneficial effects on synaptic dysfunctions and altered behavior in the AS mice model. In mutant mice, we observed impairment of the synaptic machinery of protein synthesis, which was reversed by 5-HT7R activation. Moreover, stimulation of 5-HT7R was able to: i) enhance dendritic spine density in hippocampal neurons, which was reduced in AS mice; ii) restore impaired long-term potentiation (LTP) in hippocampal slices of the AS mice; iii) improve cognitive performance of the mutant animals subjected to the fear conditioning paradigm. Altogether, our results, showing beneficial effects of 5-HT7R stimulation in restoring molecular and cognitive deficits associated with AS, suggest that targeting 5-HT7R could be a promising therapeutic approach for the pathology.

3.
Sci Rep ; 14(1): 19355, 2024 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-39169050

RESUMO

The proposition of a minimal dose of resistance training (RT) to elicit health benefits, encompassing physiological and psychological aspects, has garnered attention. While empirical investigations have demonstrated the efficacy of low-volume RT protocols in inducing adaptations such as enhanced strength and functional capacity, further exploration of the effects of this paradigm across a broader spectrum of variables is warranted. Thus, this study aimed to investigate the effects of minimal dose RT on strength and functional capacity, cardiac autonomic modulation, and hemodynamic parameters in menopausal women. Twenty-six women were randomly assigned to the training (TG: 63.2 ± 9.3 years) or control group (CG: 59.3 ± 7.6 years). Anthropometric measurements, strength and functional performance tests, cardiac autonomic assessment, and hemodynamic parameters were performed before and after four weeks of intervention. The TG performed the minimum dose RT twice weekly for four weeks (2 sets of 8-12 repetitions in three dynamic exercises, plus three 1-min isometric planks), and the CG had a weekly meeting with lectures and stretching. Two-way ANOVA with repeated measures was applied to each variable. Regarding time comparisons, there was a significant increase for LniRR (F = 4.78; ω2 = 0.046; p = 0.04), one repetition maximum (1RM) bench press (F = 8.06; ω2 = 0,013; p = 0.01), and 1RM leg press (F = 17.3; ω2 = 0,098; p < 0.01). There was a group*time interaction only for the index LnRMSSD (F = 5.11; ω2 = 0.042; p = 0.03), and 1RM bench press (F = 9.52; ω2 = 0,016; p = 0.01). No between-group main effect for any variable was found. The minimal dose RT protocol improved muscle strength, while cardiac autonomic and hemodynamic variables, as well as functional capacity, remained stable over 4 weeks in menopausal women.


Assuntos
Sistema Nervoso Autônomo , Menopausa , Força Muscular , Treinamento Resistido , Humanos , Feminino , Treinamento Resistido/métodos , Pessoa de Meia-Idade , Menopausa/fisiologia , Força Muscular/fisiologia , Sistema Nervoso Autônomo/fisiologia , Idoso , Coração/fisiologia , Frequência Cardíaca/fisiologia , Hemodinâmica/fisiologia
4.
Nutrients ; 16(12)2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38931247

RESUMO

Guarana (GUA), a Brazilian seed extract, contains caffeine and other bioactive compounds that may have psychoactive effects. To assess the acute effects of GUA compared to a low dose of caffeine (CAF) on cognitive and mood parameters, twenty participants completed a double-blind, crossover experiment where they ingested capsules containing the following: (1) 100 mg CAF, (2) 500 mg GUA containing 130 mg caffeine, or (3) placebo (PLA). Cognitive tests (Simon and 2N-Back Task) were performed at the baseline (pre-ingestion) and 60 min after ingestion. The response time for the cognitive tests and heart rate variability were unaffected (p > 0.05) by treatment, although 2N-Back was overall faster (p = 0.001) across time. The accuracy in the 2N-Back Task showed a significant interaction effect (p = 0.029) due to higher post-ingestion versus pre-ingestion levels (p = 0.033), but only with the PLA. The supplements also had no effect on cognitive measures following physical fatigue (n = 11). There was an interaction effect on perceived mental energy, where the pre-ingestion of GUA had lower mental pep ratings compared to post-ingestion (p = 0.006) and post-exercise (p = 0.018) levels. Neither the acute ingestion of GUA nor low dose of CAF influenced cognitive performance or provided consistent benefit on mood or mental workload through vagal modulation. Additional investigations are beneficial to determining the lowest effective dose for CAF or GUA to influence mood and/or cognitive performance.


Assuntos
Afeto , Cafeína , Cognição , Estudos Cross-Over , Frequência Cardíaca , Paullinia , Humanos , Cafeína/administração & dosagem , Cafeína/farmacologia , Paullinia/química , Masculino , Método Duplo-Cego , Cognição/efeitos dos fármacos , Adulto , Adulto Jovem , Feminino , Frequência Cardíaca/efeitos dos fármacos , Afeto/efeitos dos fármacos , Nervo Vago/fisiologia , Nervo Vago/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Suplementos Nutricionais
5.
Sports Med Health Sci ; 6(2): 111-122, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38708326

RESUMO

There is a recent and growing interest in assessing differential responders to resistance training (RT) for diverse outcomes. Thus, the individual ability to respond to an intervention for a specific measurement, called responsiveness, remains to be better understood. Thus, the current study aimed to summarize the available information about the effects of RT on functional performance and muscle strength, power, and size in healthy adults, through the prevalence rate in different responsiveness classifications models. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was registered at the International Prospective Register of Systematic Reviews (PROSPERO, CRD42021265378). PubMed/MEDLINE, Scopus, and Embase databases were systematically searched in October 2023. A total of 13 studies were included, totaling 921 subjects. Only two studies presented a low risk of bias. Regarding the effectiveness of RT, the prevalence rate for non-responders ranged from 0% to 44% for muscle strength, from 0% to 84% for muscle size, and from 0% to 42% for functional performance, while for muscle power, the only study found showed a responsiveness rate of 37%. In conclusion, a wide range of differential responders is described for all variables investigated. However, the evidence summarized in this systematic review suggested some caution while interpreting the findings, since the body of evidence found seems to be incipient, and widely heterogeneous in methodological and statistical aspects.

6.
J Nutr Biochem ; 128: 109624, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38518858

RESUMO

Brain plasticity and cognitive functions are tightly influenced by foods or nutrients, which determine a metabolic modulation having a long-term effect on health, involving also epigenetic mechanisms. Breast milk or formula based on cow milk is the first food for human beings, who, throughout their lives, are then exposed to different types of milk. We previously demonstrated that rats fed with milk derived from distinct species, with different compositions and nutritional properties, display selective modulation of systemic metabolic and inflammatory profiles through changes of mitochondrial functions and redox state in liver, skeletal and cardiac muscle. Here, in a rat model, we demonstrated that isoenergetic supplementation of milk from cow (CM), donkey (DM) or human (HM) impacts mitochondrial functions and redox state in the brain cortex and cortical synapses, affecting neuroinflammation and synaptic plasticity. Interestingly, we found that the administration of different milk modulates DNA methylation in rat brain cortex and consequently affects gene expression. Our results emphasize the importance of nutrition in brain and synapse physiology, and highlight the key role played in this context by mitochondria, nutrient-sensitive organelles able to orchestrate metabolic and inflammatory responses.


Assuntos
Córtex Cerebral , Metilação de DNA , Leite , Mitocôndrias , Sinapses , Animais , Córtex Cerebral/metabolismo , Leite/química , Leite/metabolismo , Mitocôndrias/metabolismo , Sinapses/metabolismo , Ratos , Masculino , Plasticidade Neuronal , Doenças Neuroinflamatórias/metabolismo , Feminino , Ratos Wistar , Bovinos
7.
Int J Sports Med ; 45(5): 369-376, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38346688

RESUMO

This study aimed to investigate the impact of bar velocity during the eccentric phase on subsequent concentric performance in the young and elderly. Twelve elderly women (65.2+4.2 years) and 16 young women (23.1+2.1 years) were randomly assigned to four experimental conditions that combined high-velocity eccentric actions (HVECC; maximum velocity) and moderate-velocity eccentric actions (MVECC; 2.0 s), using 30% and 60% of their 1-repetition maximum (1RM) on the Smith machine bench press. Measurements of mean propulsive velocity (MPV), peak velocity (PV), and mean power (MP) were recorded. Two-way ANOVA with repeated measures was applied for each variable, when needed, the Bonferroni post hoc was used. Statistical significance was set at p<0.05, and effect size (ES) was established by Cohen's d z. The results demonstrated that elderly women showed improved performance in MPV (+10.0%; ES=- 0.58; p=0.009) and MP (+11.7%; ES=- 0.14; p=0.045) when utilizing HVECC at 30% 1RM only. Moreover, young women exhibited superior performance for both 30% and 60% 1RM when using HVECC for all variables analyzed (p<0.05). The HVECC appears to have an impact on the subsequent performance of the concentric phase, particularly when lighter loads (30% 1RM) are utilized, regardless of the age group.


Assuntos
Força Muscular , Levantamento de Peso , Humanos , Feminino , Idoso , Levantamento de Peso/fisiologia , Adulto Jovem , Força Muscular/fisiologia , Fatores Etários , Treinamento Resistido/métodos , Pessoa de Meia-Idade , Adulto , Músculo Esquelético/fisiologia , Desempenho Atlético/fisiologia
8.
Int J Sport Nutr Exerc Metab ; 34(1): 30-37, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37898479

RESUMO

Guarana (GUA) seed extract, containing caffeine (CAF) and additional bioactive compounds, may positively affect mental performance, but evidence regarding exercise is limited. This investigation assessed acute GUA ingestion compared with CAF on endurance performance. Eleven endurance-trained noncyclists and cyclists (V˙O2peak = 49.7 ± 5.9, 60.4 ± 4.6 ml·kg·min-1) completed a double-blind, crossover experiment after ingesting (a) 100 mg CAF, (b) 500 mg GUA (containing 130 mg CAF), or (c) placebo (P) prior to 60-min fixed cycling workload (FIX) + 15-min time trial. Oxygen uptake, heart rate, respiratory exchange ratio, blood glucose, and lactate were not different (p ≥ .052) during FIX. A significant interaction (p = .042) for perceived exertion was observed at 50-min FIX with lower rating (p = .023) for GUA versus CAF but not compared with P. Work accumulated over 15-min time trial was greater (p = .038) for GUA versus P due to higher early (1-11 min) work outputs. Work performance favored (effect size = 0.18; 95% confidence interval [0.003, 0.355], p = .046) GUA (241.4 ± 39.9 kJ) versus P (232.1 ± 46.6 kJ), but CAF (232.3 ± 43.9) was not different from GUA (effect size = 0.19; 95% confidence interval [-0.022, 0.410], p = .079) or P. Postexercise strength loss was not attenuated with GUA (-5.6 ± 8.5%) or CAF (-8.3 ± 9.4%) versus P (-10.3 ± 5.1%). Acute GUA ingestion improved work performance relative to P, but effects were trivial to small and unrelated to altered substrate oxidation or muscular strength. Ergogenicity may involve central mechanisms reducing perceived effort with GUA (containing 130 mg caffeine). Due to issues related to identical matching of dosage, whether GUA confers additional benefits beyond its CAF content cannot be determined at present.


Assuntos
Desempenho Atlético , Paullinia , Humanos , Cafeína , Resistência Física/fisiologia , Ácido Láctico , Exercício Físico/fisiologia , Método Duplo-Cego , Estudos Cross-Over , Desempenho Atlético/fisiologia
9.
Mol Neurobiol ; 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38087165

RESUMO

Cystatin B (CSTB) is a small protease inhibitor protein being involved in cell proliferation and neuronal differentiation. Loss-of-function mutations in CSTB gene cause progressive myoclonic epilepsy 1 (EPM1). We previously demonstrated that CSTB is locally synthesized in synaptic nerve terminals from rat brain and secreted into the media, indicating its role in synaptic plasticity. In this work, we have further investigated the involvement of CSTB in synaptic plasticity, using synaptosomes from human cerebral organoids (hCOs) as well as from rodents' brain. Our data demonstrate that CSTB is released from synaptosomes in two ways: (i) as a soluble protein and (ii) in extracellular vesicles-mediated pathway. Synaptosomes isolated from hCOs are enriched in pre-synaptic proteins and contain CSTB at all developmental stages analyzed. CSTB presence in the synaptic territories was also confirmed by immunostaining on human neurons in vitro. To investigate if the depletion of CSTB affects synaptic plasticity, we characterized the synaptosomes from EPM1 hCOs. We found that the levels of presynaptic proteins and of an initiation factor linked to local protein synthesis were both reduced in EPM1 hCOs and that the extracellular vesicles trafficking pathway was impaired. Moreover, EPM1 neurons displayed anomalous morphology with longer and more branched neurites bearing higher number of intersections and nodes, suggesting connectivity alterations. In conclusion, our data strengthen the idea that CSTB plays a critical role in the synapse physiology and reveal that pathologically low levels of CSTB may affect synaptic plasticity, leading to synaptopathy and altered neuronal morphology.

10.
Int J Exerc Sci ; 16(6): 638-653, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37621711

RESUMO

This study aims to elucidate the internal load, performance, physiological, and perceptual recovery responses during four weeks of traditional judo training. Ten cadet and junior judo athletes were evaluated daily for four weeks, in which their perception of recovery, heart rate variability, handgrip strength, and countermovement jump performance were assessed. A one-way repeated-measures ANOVA was performed to analyze the variables across the weeks. A significant time effect in internal load (F = 6.51; p = 0.001) has been observed. Handgrip test performance showed significantly higher values in the 3rd and 4th weeks (p <0.001), while countermovement jump performance was significantly higher in the 4th week (p =0.0007). The heart rate variability's coefficient of variation was lower in both the 3rd and 4th weeks (p =0.02). Regarding perceptual aspects, the Hooper Index showed a significant time effect (p =0.04), but pairwise comparison did not reveal differences between weeks. The present study indicates that neuromuscular, physiological, and perceptual responses to training load alterations present different time courses. This must be considered for the adequate monitoring of training programs.

12.
PeerJ ; 11: e14764, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36743962

RESUMO

In combat sports, strikes or counter-strikes response time (RT) can be related to performance and sporting success. Moreover, training sessions are usually highly fatiguing, which is expected to impair basic skills, such as RT. Thus, this study aimed to investigate the effect of fatigue on punch and kick RTs of karate practitioners. Twelve individuals of both sexes from different levels (three yellow belts, three red belts, two orange belts, two green belts, one brown belt, and one black belt) were selected. Participants were aged 22 ± 3 years old, with a stature of 169.1 ± 6.5 cm, and a body mass of 65.5 ± 10 kg. Six visits were held with each participant. On the first 2 days, the RT of punches and kicks was measured by a validated smartphone app (TReaction). For the subsequent visits, a randomized incremental test for the upper or lower body was adopted as motor fatigue protocol, immediately followed by punches and kicks RT tests, also in random order. For induction of lower and upper body-specific muscle fatigue, the ITStriker app was used, which operates by emitting sound signals transmitted by a smartphone. One-way repeated measures ANOVA was performed, and significance was set at p ≤ 0.05. Regarding the mean punches RT, significant effects between situations for the upper (F(2,22) = 11.5; ω2 = 0.23; p < 0.001) and lower body (F(2,22) = 14.2; ω2 = 0.18; p < 0.001) fatigue protocols were found. The negative effect of the lower body fatigue protocol in punches RT was evident regardless of the order of the tests (punch RT first: Δ = 10.5%; t = 4.4; p < 0.001; d = 1.0; kick RT first: Δ = 11.4%; t = 4.8; p < 0.001; d = 1.1). Regarding mean kicks RT, significant effects were found between situations for the lower (F(2,22) = 16.6; ω2 = 0.27; p < 0.001) but not for the upper (F(2,22) = 2.3; ω2 = 0.02; p = 0.12) body fatigue protocols. Kick RTs were negatively affected by the lower body fatigue protocol regardless of the RT order applied (punch RT first: Δ = 7.5%; t = 3.0; p = 0.01; d = 0.8; kick RT first: Δ = 14.3%; t = 5.7; p < 0.001; d = 1.5). Upper body fatigue does not impair punch or kick RTs. Thus, it is concluded that the specificity of fatigue protocols and striking order should be considered while performing RT demanding techniques in karate practice. Specifically, lower body motor fatigue may impair both kicks and punches RT, which highlights the role of lower limbs in punches performance. Otherwise, upper body motor fatigue seems to induce impairments that are limited to the specific motor actions of this body segment.


Assuntos
Artes Marciais , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Atletas , Extremidade Inferior/fisiologia , Artes Marciais/fisiologia , Fadiga Muscular , Tempo de Reação
13.
Nutrients ; 15(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36678305

RESUMO

The plant extract guarana is known for its caffeine content and other bioactive ingredients, which purportedly may improve cognitive performance. Recent reviews have examined the effects of chronic supplementation of guarana in clinical populations; however, the acute effects of guarana on cognitive tasks, while of interest, have produced mixed results. Whether acute guarana ingestion improves human cognitive performance was assessed by performing a systematic review coupled with a meta-analysis. Eight placebo-controlled studies were identified and met the inclusion criteria providing data on 328 participants. The dose of guarana (37.5 to 500 mg) with reported caffeine content (4.3 to 100 mg) varied. Effect sizes (ESs) were calculated as the standardized mean difference and meta-analyses were completed using a random-effects model. The ESs for guarana averaged across a variety of cognitive measures and outcome variables were less than trivial (Hedge's g = 0.076, p = 0.14). Using a subgroup meta-analysis (Q = 12.9, p < 0.001), ESs indicating a faster response time for guarana vs. a placebo (g = 0.202, p = 0.005) differed from the accuracy measures (g = −0.077, p = 0.4) which were non-significant. For response time, guarana ingested in a capsule (g = 0.111) tended to differ (Q = 2.96, p = 0.085) compared to guarana when dissolved in liquid (g = 0.281). Meta-regression of the study ESs of overall cognitive task performance was not related to the guarana dose (R2 < 0.001) or to the time allowed prior to cognitive testing (R2 < 0.001). Acute guarana ingestion had a small effect on the response time (faster performance) during a variety of cognitive tasks without affecting the accuracy. Whether the changes were linked to the caffeine content or other bioavailable substances in guarana is unknown. Additional studies that directly compare matched doses of caffeine versus guarana are needed to understand its effects on cognitive performance.


Assuntos
Cafeína , Paullinia , Humanos , Cafeína/farmacologia , Extratos Vegetais/uso terapêutico , Tempo de Reação , Cognição
14.
Int J Exerc Sci ; 15(4): 771-782, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992500

RESUMO

This study aimed to compare the effects of high-speed resistance training (HSRT) and low-speed resistance training (LSRT) in physical fitness, and functional performance in untrained older women. Twenty-four women (62.2 ± 2.7 years old) were allocated to the HSRT or LSRT groups. The HSRT and LSRT groups underwent a similar training program [3 sets of 8 to 12 repetitions at 90% of 10 maximum repetitions] for 14 weeks, twice a week. The LSRT group performed the exercises with 3 seconds in the concentric and eccentric phases, while the HSRT group performed with the concentric phase as quickly as possible and 3 seconds in the eccentric phase. Participants completed pre-and post-training testing to assess strength, flexibility, muscle endurance, power, walking speed, functional balance, and aerobic endurance. Two-way mixed-model ANOVA with repeated measures was applied for each variable, and the Bonferroni post hoc was used when necessary. Statistical significance was set at p < 0.05. No significant group*time interactions were found for any variable. Time main-effect suggested significant improvements for the 10 RM bench press (F = 46.1; p < 0.001), 10 RM leg press (F = 49.8; p < 0.001), sit-to-stand test (F = 10.4; p = 0.004), sit and reach (F = 10.5; p = 0.004), Timed Up-and-Go (F = 29.8; p < 0.001) and 6-min walking test (F = 41.6; p < 0.001). Thus, the configurations of RT tested here were similarly efficient to improve the functional performance of untrained older women. In addition, both groups showed significant gains in muscle strength, but not in muscle power and gait speed.

15.
Appl Psychophysiol Biofeedback ; 47(3): 239-251, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35688989

RESUMO

We examined whether practice in an open skill video-game task would lead to changes in performance, attention, motivation, perceived effort, and theta, alpha, and beta waves. Specifically, we were interested on whether potential performance gains from practice would be primarily explained by the neural efficiency (i.e., cortical idling) or the neural proficiency hypothesis (i.e., mix of heightened and reduced activation across the cortex). To this end, we asked 16 novice participants (8 males and 8 females; Mage = 23.13 years) to play a Nintendo Wii video-game shooting task, namely Link's Crossbow Training. Pre-test scores, which were followed by an acquisition phase, were compared to post-test scores. Performance and subjective data were recorded for each trial and EEG data was continuously recorded using the portable EEGO System. Our findings revealed that performance increased while attention decreased at post-test, thereby confirming that practice leads to performance gains and reduces attentional overload. No changes in motivation or perceived effort were observed, perhaps because effort is a gestalt multidimension construct and video-gaming is an inherently motivating activity. EEG frequency analysis revealed that, for the most part, performance gains were accompanied by increased cortical activity across frequencies bands, thus lending primary support to the neural proficiency hypothesis. Accordingly, neurofeedback interventions to aid motor learning should teach performers not only how to silence their brains (i.e., quiescence state linked to automaticity and "flow") but also how to amplify task-relevant brain networks.


Assuntos
Encéfalo , Desempenho Psicomotor , Jogos de Vídeo , Atenção/fisiologia , Encéfalo/fisiologia , Feminino , Humanos , Masculino , Desempenho Psicomotor/fisiologia , Adulto Jovem
16.
J Sport Exerc Psychol ; 44(4): 272-285, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35613846

RESUMO

The objective of this study was to analyze the effect of anodal transcranial direct current stimulation (a-tDCS) over the motion-sensitive midtemporal area on perceptual-cognitive skills (visuomotor and basketball decision-making skills) in mentally fatigued basketball players. A total of 20 male basketball players were recruited. This was a randomized, double-blinded, and counterbalanced crossover study with two experimental conditions: a-tDCS and Sham. The participants completed the basketball decision-making task and visuomotor skill after performing a 60-min sport-based videogame task with anodal (i.e., a-tDCS) or placebo (Sham) stimulation over the motion-sensitive middle temporal area. Worse response time was observed in visuomotor skill for Sham than a-tDCS postexperiment (p < .05). There was no main condition effect for accuracy of visuomotor skill (p > .05). There was more impairment in accuracy and response time in basketball decision-making skills for the Sham condition than a-tDCS (p < .05). Notably, a-tDCS over the motion-sensitive middle temporal area removed the negative effects of mental fatigue on perceptual-cognitive skills.


Assuntos
Basquetebol , Córtex Motor , Estimulação Transcraniana por Corrente Contínua , Cognição/fisiologia , Estudos Cross-Over , Humanos , Masculino , Fadiga Mental , Córtex Motor/fisiologia
17.
ACS Chem Neurosci ; 13(4): 497-509, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-35099177

RESUMO

During the last decade, the kinetics of drug-target interaction has received increasing attention as an important pharmacological parameter in the drug development process. Several studies have suggested that the lipophilicity of a molecule can play an important role. To date, this aspect has been studied for several G protein-coupled receptors (GPCRs) ligands but not for the 5-HT7 receptor (5-HT7R), a GPCR proposed as a valid therapeutic target in neurodevelopmental and neuropsychiatric disorders associated with abnormal neuronal connectivity. In this study, we report on structure-kinetics relationships of a set of arylpiperazine-based 5-HT7R ligands. We found that it is not the overall lipophilicity of the molecule that influences drug-target interaction kinetics but rather the position of polar groups within the molecule. Next, we performed a combination of molecular docking studies and molecular dynamics simulations to gain insights into structure-kinetics relationships. These studies did not suggest specific contact patterns between the ligands and the receptor-binding site as determinants for compounds kinetics. Finally, we compared the abilities of two 5-HT7R agonists with similar receptor-binding affinities and different residence times to stimulate the 5-HT7R-mediated neurite outgrowth in mouse neuronal primary cultures and found that the compounds induced the effect with different timing. This study provides the first insights into the binding kinetics of arylpiperazine-based 5-HT7R ligands that can be helpful to design new 5-HT7R ligands with fine-tuning of the kinetic profile.


Assuntos
Receptores de Serotonina , Serotonina , Animais , Cinética , Ligantes , Camundongos , Simulação de Acoplamento Molecular , Receptores de Serotonina/metabolismo , Relação Estrutura-Atividade
18.
Antioxidants (Basel) ; 12(1)2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670866

RESUMO

Neurodegenerative diseases (NDDs) are characterized by cognitive impairment and behavioural abnormalities. The incidence of NDDs in recent years has increased globally and the pathological mechanism is not fully understood. To date, plentiful evidence has showed that metabolic alterations associated with obesity and related issues such as neuroinflammation, oxidative stress and mitochondrial dysfunction may represent an important risk factor, linking obesity and NDDs. Numerous studies have indicated a correlation between diet and brain activities. In this context, a key role is played by mitochondria located in the synaptic fraction; indeed, it has been shown that high-fat diets cause their dysfunction, affecting synaptic plasticity. In this scenario, the use of natural molecules that improve brain mitochondrial function represents an important therapeutic approach to treat NDDs. Recently, it was demonstrated that butyrate, a short-chain fatty acid is capable of counteracting obesity in an animal model, modulating mitochondrial function. The aim of this study has been to evaluate the effects of butyrate on neuroinflammatory state, oxidative stress and mitochondrial dysfunction in the brain cortex and in the synaptic fraction of a mouse model of diet-induced obesity. Our data have shown that butyrate partially reverts neuroinflammation and oxidative stress in the brain cortex and synaptic area, improving mitochondrial function and efficiency.

19.
J Strength Cond Res ; 36(2): 461-468, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31855926

RESUMO

ABSTRACT: Campos, BT, Penna, EM, Rodrigues, JGS, Mendes, TT, Maia-Lima, A, Nakamura, FY, Vieira, ÉLM, Wanner, SP, and Prado, LS. Influence of mental fatigue on physical performance, and physiological and perceptual responses of judokas submitted to the Special Judo Fitness Test. J Strength Cond Res 36(2): 461-468, 2022-Mentally fatigued athletes present impaired aerobic performance, strength endurance, and manual dexterity, despite no changes in anaerobic performance and maximal muscle strength and power. Noteworthy, the effect of mental fatigue on physical performance during high-intensity intermittent tests that require specific motor skills of fighting sports has not been investigated. Therefore, this study aimed to verify whether mental fatigue influences performance and physiological and perceptual responses of judokas subjected to a high-intensity intermittent test designed specifically and validated for judo. Each judoka performed 2 experimental trials-a control trial one and the other one after the induction of mental fatigue. These trials were scheduled in a random and balanced order. In both trials, lactate, glucose, and cortisol concentrations, the heart rate variability, and perceptual variables were collected after the initial treatment and after the Special Judo Fitness Test (SJFT). The initial treatment consisted of a 30-minute cognitive demanding task (Stroop Color test) or watching a movie (control) and was followed by the SJFT. The Stroop Color test increased the perceptions of mental fatigue and effort, without affecting motivation for subsequent testing. Unexpectedly, mentally fatigued athletes did not show reduced performance during the SJFT. Regarding the physiological variables, no significant differences were identified between the 2 experimental conditions. We conclude that physical performance measured during a specific test for judokas is not impaired by a previous 30-minute cognitive task that causes mental fatigue. In addition, this cognitive task did not influence the physiological changes induced by the specific physical test.


Assuntos
Desempenho Atlético , Artes Marciais , Teste de Esforço , Humanos , Fadiga Mental , Aptidão Física , Desempenho Físico Funcional
20.
Front Psychol ; 12: 656499, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290647

RESUMO

Background: Mental fatigue is a psychobiological state caused by extended periods of cognitive effort, and evidence suggests that mentally fatigued athletes present impaired physical performance. Different ergogenic aids have been proposed to counteract the deleterious effects of mental fatigue, but whether brain stimulation can counteract mental fatigue is still unknown. This scenario is even more obscure considering the effects of these interventions (mental fatigue induction and brain stimulation) in a very experienced population consisting of master athletes. Method: Ten master swimmers (30 ± 6 years old and 14 ± 8 years of experience) participated in the study. They underwent four experimental conditions before an 800-m freestyle test: mental fatigue with brain stimulation; mental fatigue without brain stimulation; absence of mental fatigue with brain stimulation; and absence of mental fatigue and no brain stimulation. Mental fatigue was induced by a cognitively demanding Stroop Color Test, whereas stimulation was applied on the temporal cortex. After that, the athletes swan 800 m as fast as possible and provided their ratings of perceived exertion (RPE) every 200 m. Results: Mental fatigue was effectively induced, as evidenced by a greater fatigue perception and more errors in the last blocks of the cognitive task. Mental fatigue induction did not influence performance (time to complete the swimming trial) and RPE. Similarly, brain stimulation failed to change these two parameters, regardless of mental fatigue induction. Conclusion: The prolonged physical performance of experienced master athletes is not influenced, under the present conditions, by mental fatigue induction, cerebral stimulation, and their association.

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