Neuromuscular adaptability of male and female rats to muscle unloading

Abstract

Previously, it has been shown that following muscle unloading, males and females experience different maladaptations in neuromuscular function. As a follow-up, the present investigation sought to determine if male and female neuromuscular systems demonstrated similar, or disparate morphological adaptations to muscle unloading. Twenty young adult male, and 20 young adult female rats were randomly assigned to one of two treatment protocols: muscle unloading, or control conditions. Following the 2 week intervention period, immunofluorescent procedures were used to quantify pre- and post-synaptic features of neuromuscular junctions (NMJs), and to assess myofiber profiles (size and fiber type composition) of the soleus, plantaris, and EDL muscles. A 2-way ANOVA with main effects for sex and treatment was then used to identify statistically significant (P ≤ 0.05) differences among structural parameters. Analysis of NMJs showed a consistent lack of differences between males and females. Overall, NMJs were also found to be resistant to the effects of unloading. When examining myofiber profiles, however, male myofibers were revealed to be significantly larger than female ones in each of the muscles examined. Unloading resulted in significant myofiber atrophy only in the primarily weight-bearing soleus muscle. Only the EDL showed unloading-induced differences in myofiber type distribution (Type II → I). These data indicate that different components of the neuromuscular system (NMJs, myofibers) respond uniquely to unloading, and that sex affects myofiber type profiles, but not NMJs. Moreover, it appears that only muscles that have their habitual activity patterns disturbed by unloading, i.e., the soleus, adapt to that intervention.

Partial Weight-Bearing in Female Rats: Proof of Concept in a Martian-Gravity Analog

“…While PWB led to a transient body weight loss in male rats (Mortreux et al, 2018(Mortreux et al, , 2019a,c), we did not observe any significant fluctuations of the females' body weight, either compared to the control group or to their pre-suspension baseline. This sex-based difference has been reported previously after exposure to 14 and 30 days of hindlimb unloading (Il'ina-Kakueva, 2002;David et al, 2006;Chang et al, 2018;Deschenes et al, 2018), and in our study, was further associated with a similar food intake, which was eventually greater at the end of the experiment in the PWB40 group when normalized to animals' body weight, compared to the PWB100 controls.…”

“…Indeed, testosterone has a strong anabolic role in the skeletal muscle (Herbst and Bhasin, 2004), while estradiol has been shown to inhibit muscle protein synthesis (Tipton, 2001). In Wistar rats, it has been shown that males have myofibers with greater cross-sectional area than females (Deschenes et al, 2018), and that they display a greater proportion of type 1 myofibers (Simard et al, 1987;Nakano et al, 1995;Novák et al, 2010), especially in the soleus, one of the muscles that atrophies most rapidly in response to mechanical unloading. Since unloadinginduced atrophy primarily affects oxidative (type 1) myofibers (Rosa-Caldwell and Greene, 2019), and leads to a fiber switch from type 1 to type 2 (Mortreux et al, 2019b), it is likely that partial mechanical unloading will yield different results in females compared to male rats, and thus demand for specific mitigating strategies.…”

Muscle unloading: A comparison between spaceflight and ground‐based models

“…These findings show that following 2 weeks of HU, males are more susceptible to neuromuscular synaptic dysfunction than females during fatigue but not during resting conditions . On the other hand, NMJ morphology was not affected by HU despite significant atrophy of slow‐twitch soleus and fast‐twitch EDL and plantaris muscles . This condition is in contrast to age‐related muscle loss or sarcopenia, which is characterized by coupling between NMJ dysfunction and muscle atrophy .…”

“…173 On the other hand, NMJ morphology was not affected by HU despite significant atrophy of slow-twitch soleus and fast-twitch EDL and plantaris muscles. 180 This condition is in contrast to age-related muscle loss or sarcopenia, which is characterized by coupling between NMJ dysfunction and muscle atrophy. 181,182 These studies show that females are more susceptible to disuse atrophy than males.…”

Forelimb unloading impairs glenohumeral muscle development in growing rats

“…Both male and female rats were compared together, and sex differences were not considered. Young (3-month old) male rats have shown to display greater reduction in total body mass compared to control rats over the hindlimb unloading period, while females did not 48 . The amputation group comprised of 3 male rats, whereas the other groups had at least one female, which could help explain why the amputation group displayed greater significance.…”