Increased Mitochondrial Calcium Sensitivity and Abnormal Expression of Innate Immunity Genes Precede Dopaminergic Defects in Pink1-Deficient Mice

BACKGROUND: PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca²+ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson\u27s disease (PD) display altered activity in the nigrostriatal system of Pink1⁻/⁻ mice. METHODS AND FINDINGS: Purified brain mitochondria of Pink1⁻/⁻ mice showed impaired Ca²+ storage capacity, resulting in increased Ca²+ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. A subpopulation of neurons in the substantia nigra of Pink1⁻/⁻ mice accumulated phospho-c-Jun, showing that Jun N-terminal kinase (JNK) activity is increased. Pink1⁻/⁻ mice 6 months and older displayed reduced DA levels associated with increased DA turnover. Moreover, Pink1⁻/⁻ mice had increased levels of IL-1β, IL-12 and IL-10 in the striatum after peripheral challenge with lipopolysaccharide (LPS), and Pink1⁻/⁻ embryonic fibroblasts showed decreased basal and inflammatory cytokine-induced nuclear factor kappa-β (NF-κB) activity. Quantitative transcriptional profiling in the striatum revealed that Pink1⁻/⁻ mice differentially express genes that (i) are upregulated in animals with experimentally induced dopaminergic lesions, (ii) regulate innate immune responses and/or apoptosis and (iii) promote axonal regeneration and sprouting. CONCLUSIONS: Increased mitochondrial Ca²+ sensitivity and JNK activity are early defects in Pink1⁻/⁻ mice that precede reduced DA levels and abnormal DA homeostasis and may contribute to neuronal dysfunction in familial PD. Differential gene expression in the nigrostriatal system of Pink1⁻/⁻ mice supports early dopaminergic dysfunction and shows that Pink1 deletion causes aberrant expression of genes that regulate innate immune responses. While some differentially expressed genes may mitigate neurodegeneration, increased LPS-induced brain cytokine expression and impaired cytokine-induced NF-κB activation may predispose neurons of Pink1⁻/⁻ mice to inflammation and injury-induced cell death

Lactate Equivalent for Maximal Lactate Steady State Determination in Soccer

© 2019, © 2019 SHAPE America. Purpose: The association between an overlooked classical Lactate Threshold (LT), named “Minimum Lactate Equivalent” (LEmin), with Maximal Lactate Steady State (MLSS) has been recently described with good MLSS prediction results in endurance-trained runners. This study aimed to determine the applicability of LEmin to predict MLSS in lower aerobic-conditioned individuals compared to well-established blood lactate-related thresholds (BLTs). Method: Fifteen soccer players [velocity at MLSS (MLSSV) 13.2 ± 1.0 km·h−1; coefficient of variation (CV) 7.6%] conducted a submaximal discontinuous incremental running test to determine BLTs and 3–6 constant velocity running tests to determine MLSSV. Results: LEmin did not differ from conventional LTs (p > .05) and was 24% lower than MLSS (p < .001; ES: 3.26). Among LTs, LEmin best predicted MLSSV (r = 0.83; p < .001; SEE = 0.59 km·h−1). There was no statistical difference between MLSS and estimated MLSS using LEmin prediction formula (p = .99; ES: 0.001). Mean bias and limits of agreement were 0.00 ± 0.58 km·h−1 and ±1.13 km·h−1, respectively. LEmin best predicted MLSSV (r = 0.92; p < .001; SEE = 0.54 km·h−1) in the pooled data of soccer players and endurance-trained runners of the previous study (n = 28; MLSSV range 11.2–16.5 km·h−1; CV 9.8%). Conclusion: Results support LEmin to be one of the best single predictors of MLSS. This study is the sole study providing specific operational regression equations to estimate the impractical gold standard MLSSV in soccer players by means of a BLT measured during a submaximal single-session test

Determinações e relações dos parâmetros anaeróbios do RAST, do limiar anaeróbio e da resposta lactacidemica obtida no início, no intervalo e ao final de uma partida oficial de handebol Determinations and relationships of the RAST anaerobic parameters, anaerobic threshold and lactacidemia response obtained at the beginning, interval and the end of an official handball match

O principal objetivo do presente estudo foi determinar os parâmetros anaeróbios obtidos através do RAST (Running-based Anaerobic Sprint Test) e o limiar anaeróbio de 12 atletas filiados a Federação Paulista de Handebol. Além disso, também procuramos verificar as correlações entre as variáveis do RAST, o limiar anaeróbio e a resposta lactacidemica obtida no início, no intervalo e ao final de uma partida oficial de handebol. As avaliações foram conduzidas em 2 dias. No primeiro dia, os atletas foram submetidos ao RAST e em seguida foi determinado o limiar anaeróbio de cada atleta através de um protocolo adaptado ao de Tegtbur et al. (1993). No segundo dia, durante a disputa de uma partida oficial de handebol, foram coletadas amostras de sangue para determinação das concentrações de lactato no início, no intervalo e ao final do jogo. Foi utilizado o teste Anova para dados repetidos, seguido pelo post hoc de Newman-Keuls quando necessário, com o intuito de comparar as concentrações de lactato obtidas ao longo da partida de handebol e a correspondente ao limiar anaeróbio. A análise de correlação de Pearson foi utilizada para verificar as relações entre os parâmetros anaeróbios, o limiar anaeróbio e as concentrações de lactato obtidas durante uma partida oficial de handebol. Para todos os casos o nível de significância foi pré-fixado em 5%. Não foram verificadas correlações dos parâmetros anaeróbios do RAST e do limiar anaeróbio com as respostas lactacidemicas durante a partida de handebol. De acordo com os resultados obtidos no presente estudo, podemos concluir que embora o protocolo proposto para a avaliação do limiar anaeróbio também forneça parâmetros anaeróbios e se aproxime das situações reais do jogo de handebol, não foram encontradas correlações significativas entre as variáveis determinadas na avaliação com as concentrações de lactato obtidas durante a partida oficial de handebol.<br>The main purpose of the present study was to determine the anaerobic parameters obtained by the RAST (Running-based Anaerobic Sprint Test) and the anaerobic threshold of twelve handballers affiliated with the Handball Federation of São Paulo. Moreover, we aimed to study the relationship of the RAST variables, the anaerobic threshold and the lactacidemia response obtained at the beginning, at the interval and at the end of a an official handball match. Measurements were carried out in two days. On the first day, the athletes performed the RAST and then, the anaerobic threshold was obtained by a protocol adapted from Tegtbur et al. (1993). On the second day, the athletes had blood samples collected to determine the blood lactate responses during the three different times of the handball game. Repeated measurements Anova test followed by post hoc Newman-Keuls test whenever needed, were used to compare the blood lactate concentrations during the handball match as well as that one corresponding to the anaerobic threshold. Pearson product-moment coefficient analysis was used to verify the relationships of the RAST variables, the anaerobic threshold and the blood lactate obtained at the beginning, in the middle and at the end of an official handball match. A significance level of 5% was chosen for all cases. Correlations between the RAST parameters and the anaerobic threshold with the blood lactate responses during the handball match have not been observed. According to our results, it is possible to conclude that the variables obtained by the protocol proposed to determine the anaerobic threshold did not present significant correlations with the blood lactate concentrations obtained during the official handball match

Comparison of Two Kinds of Endurance Training Programs on the Effects of the Ability to Recover in Amateur Soccer Players

Background: High intensity intermittent aerobic exercise is an elementary endurance training exercise to build soccer endurance. Many studies exist with professional soccer players. But limited research has been conducted with amateur soccer players. Objectives: The aim of this study was to compare and assess the effects of the shuttle-run method and the Hoff-track method on the ability to recover in amateur soccer players within three weeks. Patients and Methods: Two amateur soccer teams were randomly assigned to shuttle-run group (n = 24; SRG) (SRG: shuttle-run group) or Hoff-track group (n = 18; HTG) (HTG: hoff-track group). They performed 2 times/week over three weeks their program. SRG performed a 20 m high speed shuttle-run until exhaustion and HTG covered at their highest speed level an obstacle track. Before and after training the yo-yo intermittent recovery test level 2 (YYIRTL2) was conducted. Results: Significant differences were observed within (P &lt; 0.05) and between the groups (P = 0.06; ES = 0.50) in distance covering during YYIRTL2. Conclusions: Both training methods seem to improve the ability to recover in amateur soccer players within a short time period during the competition season