Muscle fatigue experienced during maximal eccentric exercise is predictive of the plasma creatine kinase (CK) response

in Scandinavian Journal of Medicine & Science in Sports (in press)

Unaccustomed eccentric exercise may cause skeletal muscle damage with an increase in plasma creatine kinase (CK) activity. Although the wide variability among individuals in CK response to standardized ... [more ▼]

Unaccustomed eccentric exercise may cause skeletal muscle damage with an increase in plasma creatine kinase (CK) activity. Although the wide variability among individuals in CK response to standardized lengthening contractions has been well described, the reasons underlying this phenomenon have not yet been understood. Therefore, this study investigated a possible correlation of the changes in muscle damage indirect markers after an eccentric exercise with the decline in muscle performance during the exercise. Twenty-seven healthy untrained male subjects performed three sets of 30 maximal isokinetic eccentric contractions of the knee extensors. The muscular work was recorded using an isokinetic dynamometer to assess muscle fatigue by means of various fatigue indices. Plasma CK activity, muscle soreness, and stiffness were measured before (pre) and one day after (post) exercise. The eccentric exercise bout induced significant changes of the three muscle damage indirect markers. Large intersubject variability was observed for all criteria measured. More interestingly, the log (CKpost/CKpre) and muscle stiffness appeared to be closely correlated with the relative work decrease (r = 0.84, r2 = 0.70 and r = 0.75, r2 = 0.56, respectively). This is the first study to propose that the muscle fatigue profile during maximal eccentric protocol could predict the magnitude of the symptoms associated with muscle damage in humans. [less ▲]

Prévention des courbatures musculaires en pratique sportive

in Prévention des lésions musculo-squelettiques chez le sportif (2013)

L’exercice excentrique, lorsqu’il est réalisé de manière intense et/ou inhabituelle, est réputé être à l’origine de diverses sensations de courbatures d’apparition retardée. Ces douleurs musculaires ... [more ▼]

L’exercice excentrique, lorsqu’il est réalisé de manière intense et/ou inhabituelle, est réputé être à l’origine de diverses sensations de courbatures d’apparition retardée. Ces douleurs musculaires, appelées DOMS pour Delayed-Onset Muscle Soreness, s’accompagnent de déficits structuro-fonctionnels pouvant persister pendant plusieurs jours. Bien qu’il disparaisse spontanément après quelques jours de récupération, le phénomène des DOMS reste problématique chez le sportif en raison des conséquences néfastes associées : perturbation de l’entraînement sportif, diminution de la performance athlétique et majoration du risque de lésions véritables en cas de poursuite d’activités sportives. Il apparaît donc essentiel, pour un sportif soumis à un entraînement excentrique, d’échapper aux DOMS. La mise au point d’approches susceptibles de réduire les conséquences néfastes des DOMS a constitué un objectif prioritaire de nombreuses études. Ainsi, les premiers essais ont été basés sur des stratégies nutritionnelles ou pharmacologiques ainsi que sur des procédés cliniques. Bien que certains procédés tels que le massage ou les apports nutritionnels puissent influencer de manière positive l’un ou l’autre symptôme, ceux-ci ne semblent pas capables d’agir sur le phénomène des DOMS dans sa globalité. Actuellement, la seule démarche préventive réellement efficace reste la réalisation d’un entraînement excentrique à intensité sous-maximale progressivement intensifiées. [less ▲]

Mesenchymal stem cells and neural crest stem cells from adult bone marrow: characterization of their surprising similarities and differences.

in Cellular and Molecular Life Sciences : CMLS (2012), 69(15), 2593-2608

The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The ... [more ▼]

The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crest stem cells (NCSC) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSC), including their similarities and differences. In this paper, using transcriptomic as well as proteomic technologies, we compared NCSC to MSC and stromal nestin-positive cells, all of them isolated from adult bone marrow. We demonstrated that the nestin-positive cell population, which was the first to be described as able to differentiate into functional neurons, was a mixed population of NCSC and MSC. More interestingly, we demonstrated that MSC shared with NCSC the same ability to truly differentiate into Tuj1-positive cells when co-cultivated with paraformaldehyde-fixed cerebellar granule neurons. Altogether, those results suggest that both NCSC and MSC can be considered as important tools for cellular therapies in order to replace neurons in various neurological diseases. [less ▲]

Muscle fatigue experienced during maximal eccentric exercise is predictive of the plasma creatine kinase (CK) response

in Meeusen, R.; Duchateau, J.; Roelands, B. (Eds.) et al Book of Abstracts of the 17th annual Congress of the ECSS (2012, July)

Identification of protein networks involved in the disease course of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis.

in PLoS ONE (2012), 7(4), 35544

A more detailed insight into disease mechanisms of multiple sclerosis (MS) is crucial for the development of new and more effective therapies. MS is a chronic inflammatory autoimmune disease of the ... [more ▼]

A more detailed insight into disease mechanisms of multiple sclerosis (MS) is crucial for the development of new and more effective therapies. MS is a chronic inflammatory autoimmune disease of the central nervous system. The aim of this study is to identify novel disease associated proteins involved in the development of inflammatory brain lesions, to help unravel underlying disease processes. Brainstem proteins were obtained from rats with MBP induced acute experimental autoimmune encephalomyelitis (EAE), a well characterized disease model of MS. Samples were collected at different time points: just before onset of symptoms, at the top of the disease and following recovery. To analyze changes in the brainstem proteome during the disease course, a quantitative proteomics study was performed using two-dimensional difference in-gel electrophoresis (2D-DIGE) followed by mass spectrometry. We identified 75 unique proteins in 92 spots with a significant abundance difference between the experimental groups. To find disease-related networks, these regulated proteins were mapped to existing biological networks by Ingenuity Pathway Analysis (IPA). The analysis revealed that 70% of these proteins have been described to take part in neurological disease. Furthermore, some focus networks were created by IPA. These networks suggest an integrated regulation of the identified proteins with the addition of some putative regulators. Post-synaptic density protein 95 (DLG4), a key player in neuronal signalling and calcium-activated potassium channel alpha 1 (KCNMA1), involved in neurotransmitter release, are 2 putative regulators connecting 64% of the identified proteins. Functional blocking of the KCNMA1 in macrophages was able to alter myelin phagocytosis, a disease mechanism highly involved in EAE and MS pathology. Quantitative analysis of differentially expressed brainstem proteins in an animal model of MS is a first step to identify disease-associated proteins and networks that warrant further research to study their actual contribution to disease pathology. [less ▲]

Reproductive impact and proteomic analysis of androgenic and anti-androgenic disruptors on the hermaphroditic freshwater gastropod Lymnaea stagnalis

Poster (2011, November)

In this study, e ects of two androgens (tributyltin and testosterone), one antiandrogen (cyproterone acetate) and one estrogen (chlordecone) on growth and reproduction were investigated in the ... [more ▼]

In this study, e ects of two androgens (tributyltin and testosterone), one antiandrogen (cyproterone acetate) and one estrogen (chlordecone) on growth and reproduction were investigated in the hermaphrodite gastropod Lymnaea stagnalis. In this study, exposure to a range of concentrations (ng/l to μg/l) of each chemical was performed during 21 days. e number of clutches and the number of eggs per clutch were monitored. A decrease in clutches laid per snail was observed after exposure to tributyltin (540, 1180 and 2600 ng/l) and chlordecone (10, 22, 50 and 110 μg/l). A signi cant decrease in egg laid per snail was observed after exposure to tributyltin (540, 1180 and 2600 ng/l) and chlordecone (50 and 110 μg/l). An increase of egg abnormalities ratio in exposed snails (atrophied albumen, polyembryonicity,...) was observed in L. stagnalis following exposure to testosterone (2, 22, 50 and 110 ng/l), cyproterone acetate (4,5 and 50 μg/l), tributyltin (110 and 244 ng/l) and chlordecone (4,5 and 10 μg/l). Investigation of alteration in protein expression in exposed snails was performed using proteomic analysis such as 2D-DIGE. Mass spectrometry identi cation was performed on proteins with altered expression. We could establish correlation between reproductive endpoints and changes in proteins involved in egg formation and in egg laying were underlined. Egg yolk ferritin, the main protein of egg yolk, was shown to be reduced signi cantly in relationship with a decrease of egg yolk quality after exposure to tributyltin 540 ng/l and cyproterone acetate 4,5 μg/l. Ovipostatin, a protein proved to reduce egg masses, was signi cantly over expressed in snails exposed to 50 μg/l of chlordecone and were in relationship with a reduction of clutches laid by individuals. Further western blot analysis on those proteins involved in the reproduction are underway. ese analysis will enable us to con rm and re ne with more speci city the 2D-DIGE results for the selected proteins. e results of this study can help to establish new biomarkers of exposure of endocrine disruptors in freshwater environment and can provide new insight on mode of action of endocrine disruptors in L. stagnalis. [less ▲]

Update in the methodology of the chronic stress paradigm: internal control matters

in Behavioral and Brain Functions : BBF (2011), 7

To date, the reliability of induction of a depressive-like state using chronic stress models is confronted by many methodological limitations. We believe that the modifications to the stress paradigm in ... [more ▼]

To date, the reliability of induction of a depressive-like state using chronic stress models is confronted by many methodological limitations. We believe that the modifications to the stress paradigm in mice proposed herein allow some of these limitations to be overcome. Here, we discuss a variant of the standard stress paradigm, which results in anhedonia. This anhedonic state was defined by a decrease in sucrose preference that was not exhibited by all animals. As such, we propose the use of non-anhedonic, stressed mice as an internal control in experimental mouse models of depression. The application of an internal control for the effects of stress, along with optimized behavioural testing, can enable the analysis of biological correlates of stressinduced anhedonia versus the consequences of stress alone in a chronic-stress depression model. This is illustrated, for instance, by distinct physiological and molecular profiles in anhedonic and non-anhedonic groups subjected to stress. These results argue for the use of a subgroup of individuals who are negative for the induction of a depressive phenotype during experimental paradigms of depression as an internal control, for more refined modeling of this disorder in animals [less ▲]

Potential Therapeutic Target Discovery by 2D-DIGE Proteomic Analysis in Mouse Models of Asthma

in Journal of Proteome Research (2011), 10(9), 4291-4301

As asthma physiopathology is complex and not fully understood to date; it is expected that new key mediators are still to be unveiled in this disease. The main objective of this study was to discover ... [more ▼]

As asthma physiopathology is complex and not fully understood to date; it is expected that new key mediators are still to be unveiled in this disease. The main objective of this study was to discover potential new target proteins with a molecular weight >20 kDa by using two-dimensional differential in-gel electrophoresis (2D-DIGE) on lung parenchyma extracts from control or allergen-exposed mice (ovalbumin). Two different mouse models leading to the development of acute airway inflammation (5 days allergen exposure) and airway remodeling (10 weeks allergen exposure) were used. This experimental setting allowed the discrimination of 33 protein spots in the acute inflammation model and 31 spots in the remodeling model displaying a differential expression. Several proteins were then identified by MALDI-TOF/TOF MS. Among those differentially expressed proteins, PDIA6, GRP78, Annexin A6, hnRPA3, and Enolase display an increased expression in lung parenchyma from mice exposed to allergen for 5 days. Conversely, Apolipoprotein A1 was shown to be decreased after allergen exposure in the same model. Analysis on lung parenchyma of mice exposed to allergens for 10 weeks showed decreased calreticulin levels. Changes in the levels of those different mediators were confirmed by Western blot and immunohistochemical analysis. Interestingly, alveolar macrophages isolated from lungs in the acute inflammation model displayed enhanced levels of GRP78. Moreover, intratracheal instillation of anti-GRP78 siRNA in allergen-exposed animals led to a decrease in eosinophilic inflammation and bronchial hyperresponsiveness. This study unveils new mediators of potential importance that are up- and down-regulated in asthma. Among up-regulated mediators, GRP-78 appears as a potential new therapeutic target worthy of further investigations. [less ▲]

Dynamics of the Dictyostelium discoideum mitochondrial proteome during vegetative growth, starvation and early stages of development

in Proteomics (2010), 9

In this study a quantitative comparative proteomics approach has been used to analyze the D. discoideum mitochondrial proteome variations during vegetative growth, starvation and the early stages of ... [more ▼]

In this study a quantitative comparative proteomics approach has been used to analyze the D. discoideum mitochondrial proteome variations during vegetative growth, starvation and the early stages of development. Application of 2D-DIGE technology allowed the detection of around 2000 protein spots on each two-dimensional gel with 180 proteins exhibiting significant changes in their expression level. In total, 96 proteins (51 unique and 45 redundant) were unambiguously identified. We show that the D. discoideum mitochondrial proteome adaptations mainly affect energy metabolism enzymes (the Krebs cycle, anaplerotic pathways, the oxidative phosphorylation system and energy dissipation), proteins involved in developmental and signalling processes as well as in protein biosynthesis and fate. The most striking observations were the opposite regulation of expression of citrate synthase and aconitase and the very large variation in the expression of the alternative oxidase (AOX) that highlighted the importance of citrate and AOX in the physiology of the development of D. discoideum. Mitochondrial energy states measured in vivo with MitoTracker Orange CMTMRos showed an increase in mitochondrial membrane polarisation during D. discoideum starvation and starvation-induced development. [less ▲]

Proteomic and functional characterization of a Chlamydomonas reinhardtii mutant lacking the mitochondrial alternative oxidase 1

in Journal of Proteome Research (2010)

In the present work we have isolated by RNA interference and characterized at the functional and the proteomic levels a Chlamydomonas reinhardtii strain devoid of the mitochondrial alternative oxidase ... [more ▼]

In the present work we have isolated by RNA interference and characterized at the functional and the proteomic levels a Chlamydomonas reinhardtii strain devoid of the mitochondrial alternative oxidase (AOX). The AOX-deficient strain displays a doubling of the cell volume and biomass without any alteration of the generation time, a significantly higher ROS production, no change in total respiration rate, and a slight decrease of the photosynthesis efficiency. In order to identify the molecular adaptation underlying these phenotypical effects, we carried out a comparative proteomic study at the level of the mitochondrial and cellular soluble proteomes. Our results indicate a strong up-regulation of the ROS scavenging systems and important modifications of proteins involved in the primary metabolism, namely an increase of enzymes involved in anabolic pathways and a concomitant general down-regulation of enzymes of the main catabolic pathways. [less ▲]