Non-invasive muscle contraction assay to study rodent models of sarcopenia

<p>Abstract</p> <p>Background</p> <p>Age-related sarcopenia is a disease state of loss of muscle mass and strength that affects physical function and mobility leading to falls, fractures, and disability. The need for therapies to treat age-related sarcopenia has attracted intensive preclinical research. To facilitate the discovery of these therapies, we have developed a non-invasive rat muscle functional assay system to efficiently measure muscle force and evaluate the efficacy of drug candidates.</p> <p>Methods</p> <p>The lower leg muscles of anesthetized rats are artificially stimulated with surface electrodes on the knee holders and the heel support, causing the lower leg muscles to push isometric pedals that are attached to force transducers. We developed a stimulation protocol to perform a fatigability test that reveals functional muscle parameters like maximal force, the rate of fatigue, fatigue-resistant force, as well as a fatigable muscle force index. The system is evaluated in a rat aging model and a rat glucocorticoid-induced muscle loss model</p> <p>Results</p> <p>The aged rats were generally weaker than adult rats and showed a greater reduction in their fatigable force when compared to their fatigue-resistant force. Glucocorticoid treated rats mostly lost fatigable force and fatigued at a higher rate, indicating reduced force from glycolytic fibers with reduced energy reserves.</p> <p>Conclusions</p> <p>The involuntary contraction assay is a reliable system to assess muscle function in rodents and can be applied in preclinical research, including age-related sarcopenia and other myopathy.</p

Quantitative MRI water content mapping of porcine intervertebral disc during uniaxial compression

International audienceBackground: Intervertebral disc (IVD) diseases are major public health problem in industrialized countries where they affect a large proportion of the population. In particular, IVD degeneration is considered to be one of the leading causes of pain consultation and sick leave. The aim of this study was to develop a new method for assessing the functionality of IVD in order to diagnose IVD degeneration. Methods: For this purpose, we have designed a specific device that enables to mechanically load porcine IVD ex vivo in the 4.7-Tesla horizontal superconducting magnet of a magnetic resonance (MR) scanner. Proton density weighted imaging (rho(H)-MRI) of the samples was acquired. Findings: The post-processing on MR images allowed (1) to reconstruct the 3D deformation under a known mechanical load and (2) to infer the IVD porosity assuming an incompressible poroelastic model. Interpretation: This study demonstrates the ability to follow the change in morphology and hydration of an IVD using MR measurements, thereby providing valued information for a better understanding of IVD function

Étude du comportement poroélastique incompressible d’un disque intervertébral sous chargement externe

Le Disque InterVertébral (DIV) est un fibrocartilage hétérogène qui assure d’une part la mobilité du rachis et d’autre part la distribution des contraintes mécaniques entre les vertèbres. Ces deux propriétés principales sont liées à la fois au contenu hydrique et à la présence des protéoglycanes (PG) dans le DIV. Les contenus en eau et en PGs diminuent selon un processus naturel durant la vie. Ce processus dégénératif est dans certains cas accéléré et conduit à des maladies dégénératives. Plusieurs études [M. Alini, S.M. Eisenstein, K. Ito, C. Little, A. Kettler, K. Masuda, J. Melrose, J. Ralphs, I. Stokes, H.J. Wilke, Eur. Spine J. 17 (2008) 2–19; E.C. Bass, N.A. Duncan, J.S. Hariharan, J. Dusick, H.U. Bueff, J.C. Lotz, Spine (Phila. Pa. 1976) 22 (1997) 2867–2876; H. Ohshima, H. Tsuji, N. Hirano, H. Ishihara, Y. Katoh, H. Yamada, Spine (Phila. Pa. 1976) 14 (1989) 1234–1244; N.D. Panagiotacopulos, Spine (Phila. Pa. 1976) 12 (1987) 912–918; N.D. Panagiotacopulos, Spine (Phila. Pa. 1976) 12 (1987) 918–924] ont montré l’importance de la teneur en eau du DIV sur son comportement biomécanique. Le but de notre étude est de suivre, avec une méthode d’Imagerie de Résonance Magnétique (IRM), les variations de morphologie et d’hydratation sous un chargement mécanique. Les campagnes de mesure complétées par un post-traitement ont permis de reconstruire la déformation volumique du DIV et d’obtenir ainsi l’évolution de la porosité au cours du chargement. Les résultats ainsi obtenus sont conformes avec la littérature et le comportement retenu adhère parfaitement avec le cadre expérimental. Ce travail d’exploration de la viabilité discale permettra d’apporter des informations importantes dans la compréhension du comportement osmotico-mécanique du DIV

Characterization of the eosinophilic myositis caused by CAPN3 mutations on a mouse model

22nd International Annual Congress of the World-Muscle-Society (WMS), Saint Malo, FRANCE, OCT 03-07, 2017International audienc

A strictly noninvasive MR setup dedicated to longitudinal studies of mechanical performance, bioenergetics, anatomy, and muscle recruitment in contracting mouse skeletal muscle

1522-2594 (Electronic) 0740-3194 (Linking) Journal Article Research Support, Non-U.S. Gov'tMR techniques have proven their ability to investigate skeletal muscle function in situ. Their benefit in terms of noninvasiveness is, however, lost in animal research, given that muscle stimulation and force output measurements are usually achieved using invasive surgical procedures, thereby excluding repeated investigations in the same animal. This study describes a new setup allowing strictly noninvasive investigations of mouse gastrocnemius muscle function using (1)H-MRI and (31)P-MR spectroscopy. Its originality is to integrate noninvasive systems for inducing muscle contraction through transcutaneous stimulation and for measuring mechanical performance with a dedicated ergometer. In order to test the setup, muscle function was investigated using a fatiguing stimulation protocol (6 min of repeated isometric contractions at 1.7 Hz). T(2)-weighted imaging demonstrated that transcutaneous stimulation mainly activated the gastrocnemius. Moreover, investigations repeated twice with a 7-day interval between bouts did show a high reproducibility in measurements with regard to changes in isometric force and energy metabolism. In conclusion, this setup enables us for the first time to access mechanical performance, energy metabolism, anatomy, and physiology strictly noninvasively in contracting mouse skeletal muscle. The possibility for implementing longitudinal studies opens up new perspectives in many research areas, including ageing, pharmaceutical research, and gene and cell therapy

Downregulation of uncoupling protein-3 in vivo is linked to changes in muscle mitochondrial energy metabolism as a result of capsiate administration.

Although it has been suggested that the skeletal muscle mitochondrial uncoupling protein-3 (UCP3) is involved in regulating energy expenditure, its role is still poorly understood. In the present study, we aimed at investigating noninvasively, using magnetic resonance techniques, metabolic changes occurring in exercising muscle as a result of capsiate treatment, which has been previously linked to UCP3 upregulation. We showed that capsiate ingestion strongly reduced UCP3 gene expression in rat gastrocnemius muscle. This large underexpression was accompanied by a significant increase in the rate of mitochondrial ATP production and phosphocreatine level both at rest and during muscle stimulation. Similarly, the stimulation-induced ATP fall and ADP accumulation were significantly less after capsiate administration than in untreated rats. The larger oxidative ATP production rate could not be explained by a proportional decrease in the anaerobic component, i.e., glycolysis and phosphocreatine breakdown. In addition, the mechanical performance was not affected by capsiate administration. Finally, the plasma free fatty acid (FFA) level increased in capsiate-treated rats, whereas no significant change was observed after muscle stimulation in the control group. Considering the corresponding enhanced UCP3 mRNA expression occurring in the control group after muscle stimulation, one can suggest that changes in FFA level and UCP3 mRNA expression are not mechanistically correlated. Overall, we have shown that capsiate administration induced a UCP3 downregulation coupled with an increased mitochondrial ATP synthesis, whereas the muscle force-generating capacity was unchanged. This suggests that a decrease in muscle efficiency and/or additional noncontractile ATP-consuming mechanisms result from UCP3 downregulation

Beneficial effects of citrulline malate on skeletal muscle function in endotoxemic rat

International audienc