Alteration of performance in a mouse model of Emery-Dreifuss muscular dystrophy caused by A-type lamins gene mutation.

Autosomal Emery-Dreifuss muscular dystrophy (EDMD) is caused by mutations in the lamin A/C gene (LMNA) encoding A-type nuclear lamins, intermediate filament proteins of the nuclear envelope. Classically, the disease manifests as scapulo-humero-peroneal muscle wasting and weakness, early joint contractures and dilated cardiomyopathy with conduction blocks; however, variable skeletal muscle involvement can be present. Previously, we and other demonstrated altered activity of signaling pathways in hearts and striated muscles of LmnaH222P/H222P mice, a model of autosomal EDMD. We showed that blocking their activation improved cardiac function. However, the evaluation of the benefit of these treatments on the whole organism is suffering from a better knowledge of the performance in mouse models. We show in the present study that LmnaH222P/H222P mice display a significant loss of lean mass, consistent with the dystrophic process. This is associated with altered VO2 peak and respiratory exchange ratio. These results showed for the first time that LmnaH222P/H222P mice have decreased performance and provided a new useful means for future therapeutic interventions on this model of EDMD.

A Mouse Model of Cardiomyopathy Induced by Mutations in the Hemochromatosis HFE Gene.

BACKGROUND: The heart is 1 of the organs most affected by hereditary hemochromatosis (HH). The clinical impact of cardiomyopathy in patients with HH requires a particular diagnosis and less invasive treatments. We developed a model of cardiomyopathy in knockout (KO) mice for the high-Fe (HFE) gene and assessed left ventricular (LV) function and structure from 7-20 months. METHODS: Male wild-type (WT) heterozygous and KO SV129 mice for the HFE gene were used in this study. Twenty-four mice were used to assess LV function and structure by echocardiography at 7, 14, 18, and 20 months. Evaluations of LV function and structure and myocardial fibrosis were performed at 7 and 20 months. RESULTS: The percent decrease of LV thickness-to-radius ratio between 7 and 20 months was higher in KO mice compared with WT mice (-30.2% ± 5.3% vs -10.5% ± 4.9%; P < 0.01). The LV diameters were higher in old mice compared with young mice (+13% at end-diastole; +33% at end-systole; P < 0.001). The LV ejection fraction values were lower in KO mice compared with WT mice between 7 and 20 months. The highest difference was found at 14 months (60.0% ± 7.6% vs 78.1% ± 3.5%; P < 0.001). Myocardial fibrosis was higher in old KO mice compared with old WT mice (+55%; P < 0.001), and myocardial iron deposition was slightly increased in old KO mice compared with old WT mice (1.31% ± 0.33% vs 0.84% ± 0.22%; P = 0.056). CONCLUSIONS: The present mouse model has the potential to allow the determination of underlying mechanisms involved in the cardiomyopathy induced by HFE-related hemochromatosis.

Effect of constitutive inactivation of the myostatin gene on the gain in muscle strength during postnatal growth in two murine models.

INTRODUCTION: The effect of constitutive inactivation of the gene encoding myostatin on the gain in muscle performance during postnatal growth has not been well characterized. METHODS: We analyzed 2 murine myostatin knockout (KO) models, (i) the Lee model (KOLee ) and (ii) the Grobet model (KOGrobet ), and measured the contraction of tibialis anterior muscle in situ. RESULTS: Absolute maximal isometric force was increased in 6-month-old KOLee and KOGrobet mice, as compared to wild-type mice. Similarly, absolute maximal power was increased in 6-month-old KOLee mice. In contrast, specific maximal force (relative maximal force per unit of muscle mass was decreased in all 6-month-old male and female KO mice, except in 6-month-old female KOGrobet mice, whereas specific maximal power was reduced only in male KOLee mice. CONCLUSIONS: Genetic inactivation of myostatin increases maximal force and power, but in return it reduces muscle quality, particularly in male mice. Muscle Nerve 55: 254-261, 2017.

Prediction of one-repetition maximum from submaximal ratings of perceived exertion in older adults pre- and post-training.

BACKGROUND: Individual's one-repetition maximum (1-RM) is required to calculate and prescribe intensity for resistance training, while testing protocols enhance the risk of injuries and are time-consuming. AIMS: The aim of the present study was to assess the accuracy of 1-RM prediction from ratings of perceived exertion (RPE) of resistance exercises performed at submaximal sets (intensity and volume) in older adult males before and after a 12-week rehabilitation program. METHODS: 18 untrained subjects (70.4 ± 4.5 years) first completed a 1-RM direct assessment with a horizontal leg press pre- and post-training. Thereafter, participants performed, in a random order, 2-repetition sets with loads unknown to them (corresponding to 20, 45 and 70 % of 1-RM). The RPE was recorded immediately after the sets. That RPE associated to its corresponding load was subjected to a linear regression analysis to extrapolate the maximal RPE score and its corresponding 1-RM. RESULTS: RPE and relative intensities of sets appeared related pre- [r (2) = 0.59, standard error of estimate (SEE) = 13.3 %] and post-training (r (2) = 0.83, SEE = 8.1 %). Differences between measured and predicted 1-RM were reduced from the beginning to the end of training but standard deviations remained high (17.4 ± 11.8 vs. 4.2 ± 11.1 kg). Pre-training, 1-RM expressed relatively to body weight was negatively related with the errors of 1-RM predictions (r (2) = 0.39, p = 0.03). CONCLUSIONS: In older subjects, RPE may be used to predict 1-RM; however, the predicted value deviates considerably from the measured one, necessitating cautious application. Importantly, this method allows to capture training-induced change in 1-RM, thus making possible assessing training's effectiveness and allowing its modification if necessary.

Short-term glucocorticoid intake improves exercise endurance in healthy recreationally trained women.

The present study investigated whether short-term oral administration of glucocorticoid would modify performance and selected hormonal and metabolic parameters during submaximal exercise in healthy women. Nine recreational female athletes completed cycling trials at 70-75% VO(2) max until exhaustion after either placebo (Pla, gelatin) or oral prednisone (Cor, Cortancyl, 50 mg per day for 1 week) treatment, according to a double-blind and randomized protocol. Blood samples were collected at rest; after 10, 20, and 30 min of exercise; at exhaustion; and after 10 and 20 min of passive recovery for adrenocorticotrophic hormone (ACTH), dehydroepiandrosterone (DHEA), prolactin (PRL), growth hormone (GH), insulin (Ins), blood glucose (Glu), and lactate (Lac) determination. Cycling time was significantly increased with short-term Cor intake (Cor: 66.4 +/- 8.4 vs. Pla: 47.9 +/- 6.7 min, P < 0.01). ACTH and DHEA remained completely blunted throughout the experiment with Cor versus Pla (P < 0.01), whereas GH and PRL were significantly decreased with Cor after, respectively, 20 and 30 min of exercise (P < 0.05). No significant difference in Ins or Glu values was found between the two treatments but Lac concentrations were significantly increased with Cor versus Pla between 10 and 30 min of exercise (P < 0.05). These data indicate that short-term glucocorticoid intake improved endurance performance in women, but further investigation is needed to determine whether these results are applicable to elite female athletes and, if so, current WADA legislation needs to be changed.