Resveratrol treatment reduces the appearance of tubular aggregates and improves the resistance to fatigue in aging mice skeletal muscles

Resveratrol (RES) is a polyphenolic compound found in grapes, peanuts, and in some berries. RES has been reported to exhibit antioxidant, anti-inflammatory, anti-proliferative properties, and to target mitochondrial- related pathways in mammalian cells and animal models. Therefore, RES is currently advised as supplement in the diet of elderly individuals. Although it is hypothesized that some of RES beneficial actions likely arise from its action on the skeletal muscle, the investigation of RES effects on this tissue remains still elusive. This study reports the effects of a 0,04% RES-supplemented diet for six months, on the skeletal muscle properties of C57/ BL6 aging mice. The analysis of the morphology, protein expression, and functional-mechanical properties of selected skeletal muscles in treated compared to control mice, revealed that treated animals presented less tubular aggregates and a better resistance to fatigue in an ex-vivo contraction test, suggesting RES as a good candidate to reduce age-related alterations in muscle

Malignant Hyperthermia and Heat Stroke in Calsequestrin-1 Knockout Mice

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Initial Characterization of CASQ1/CASQ2 Knockout (double CASQ-Null) Mice

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Estrogens Protect Calsequestrin-1 Knockout Mice from Lethal Hyperthermic Episodes by Reducing Oxidative Stress in Muscle

Oxidative stress has been proposed to play a key role in malignant hyperthermia (MH), a syndrome caused by excessive Ca2+ release in skeletal muscle. Incidence of mortality in male calsequestrin-1 knockout (CASQ1-null) mice during exposure to halothane and heat (a syndrome closely resembling human MH) is far greater than that in females. To investigate the possible role of sex hormones in this still unexplained gender difference, we treated male and female CASQ1-null mice for 1 month, respectively, with Premarin (conjugated estrogens) and leuprolide (GnRH analog) and discovered that during exposure to halothane and heat Premarin reduced the mortality rate in males (79–27% and 86–20%), while leuprolide increased the incidence of mortality in females (18–73% and 24–82%). We then evaluated the (a) responsiveness of isolated muscles to temperature and caffeine, (b) sarcoplasmic reticulum (SR) Ca2+ release in single fibers, and (c) oxidative stress and the expression levels of main enzymes involved in the regulation of the redox balance in muscle. Premarin treatment reduced the temperature and caffeine sensitivity of EDL muscles, normalized SR Ca2+ release, and reduced oxidative stress in males, suggesting that female sex hormones may protect mice from lethal hyperthermic episodes by reducing both the SR Ca2+ leak and oxidative stress