Effects of alcohol on skeletal muscle contractile performance in male and female mice

Abstract

Background Acute and chronic alcohol use can cause skeletal muscle myopathy in concert with impairments in skeletal muscle strength, function and fatigue resistance. However, the fundamental contractile deficits induced in the presence of alcohol versus those observed in the recovery period following the clearance of alcohol have not yet been characterized nor is it known whether sex influences these outcomes. Methods Male and female mice received an intraperitoneal injection of either saline (Control) or ethanol (EtOH; 5g/kg body weight). Muscle force, fatigue, fatigue recovery and twitch characteristics of the posterior crural muscle complex were measured in situ 1 hour and 24 hours post alcohol. Results In the presence of alcohol (1-hour post treatment) absolute and normalized force generated at 80–150 Hertz was decreased in male and female mice with concurrent reductions in the rate of force development and increases in ½ relaxation time. When expressed as a percentage of maximum force, both males and females also displayed an alcohol-induced leftward shift in the force frequency curve indicative of a type I contractile phenotype. Alcohol enhanced fatigue in both males and females but had no effect on force recovery. Following clearance of alcohol (24-hour post treatment), contractile function was completely restored in females while alcohol treated males experienced sustained reductions in absolute force and had enhanced fatigue compared with male controls. Conclusions In the presence of alcohol, both males and females exhibited significant declines in muscle force production and enhanced fatigue; however, following complete clearance of the alcohol, females recovered all functional parameters, while males did not.

The electrophysiological properties of hindlimb motoneurons do not differ between male and female rats

“…This study found no significant difference in the basic electrophysiological properties of male and female rat MNs. These results were unexpected, given the numerous studies that indicate considerable sexual dimorphism in muscle mass, morphology, motor innervation, fibre biochemical composition and motor unit contractility (Celichowski & Drzymała‐Celichowska, 2007; Drzymała‐Celichowska & Krutki, 2015; Eason et al, 2000; English et al, 1999; English & Widmer, 2003; Mierzejewska‐Krzyżowska et al, 2011), which appear to be essential for the obvious differences in motor performance observed between male and female animals (Laudato et al, 2021; Mortreux et al, 2021) and humans (Hicks et al, 2001; Roberts et al, 2020). Differences between sexes in the electrophysiological properties of MNs would have a significant impact on the recruitment of motor units and the rate of force development during contractions.…”

Episodic Binge-like Ethanol Reduces Skeletal Muscle Strength Associated with Atrophy, Fibrosis, and Inflammation in Young Rats

“…One limitation of the mentioned study was the measure of muscle function in isolated muscle, which did not consider the critical physiological environment of the tissue, such as vascularization, oxygenation, and the contribution of the motor neuron and neuromuscular junction (NMJ) synaptic transmission, which might be affected by the presence of ethanol [ 87 ]. More recently, Laudato et al compared male and female mice for 1 h and 24 h after administering a binge-like dose of ethanol (5 g/kg) [ 25 ]. They used an in situ approximation, which better maintained the physiological muscle environment, and they found that both males and females exposed to binge ethanol exhibited a reduction in force production and enhanced muscle fatigue 1h after ethanol administration; however, only females recovered after 24 h of ethanol clearance, while males still presented some contractile deficits [ 25 ].…”

“…More recently, Laudato et al compared male and female mice for 1 h and 24 h after administering a binge-like dose of ethanol (5 g/kg) [ 25 ]. They used an in situ approximation, which better maintained the physiological muscle environment, and they found that both males and females exposed to binge ethanol exhibited a reduction in force production and enhanced muscle fatigue 1h after ethanol administration; however, only females recovered after 24 h of ethanol clearance, while males still presented some contractile deficits [ 25 ]. Nevertheless, and despite the possible differences between rats and mice, in both mentioned studies the binge protocol consisted of a single exposure, and contractile function was measured between 1 to 24 h after ethanol administration [ 24 , 25 ].…”

“…In the last few years, a few studies in murine models have evaluated contractile properties under ethanol doses equivalent to BD. However, the BD model consisted of a single administration in those studies, and contractile function was measured 2 h [ 24 ], or 1 and 24 h [ 25 ] after ethanol administration. Therefore, cellular and molecular alterations leading to functional damage upon ethanol consumption/administration that might take longer to develop would be unnoticed from those observations.…”

Alcohol Induces Zebrafish Skeletal Muscle Atrophy through HMGB1/TLR4/NF-κB Signaling

“…Body weight, lean body mass, and skeletal muscle weight/whole body weight loss, as obvious markers of skeletal muscle atrophy, are commonly observed in models of alcohol-induced skeletal muscle atrophy [ 35 , 36 , 37 ]. Decreased muscle strength and increased perception of exercise fatigue have been reported in alcohol-fed mice [ 38 ]. In this experiment, zebrafish’s body weight, back muscle/body weight, and skeletal muscle fiber cross-sectional area were significantly reduced.…”