Increasingly it has become apparent that the neuromuscular system - like other vital physiological systems - displays sexually dimorphic characteristics in structure (fiber size and fiber type composition) and function (bioenergetic pathways and resistance to fatigue). More recently, evidence has shown that men and women also experience different adaptations to muscle unloading. That is, women experience significantly greater unloading induced declines in muscle function than men. To date, the evidence suggests that the greater sensitivity of women to muscle unloading is related to more pronounced decrements in neural activation of muscle (i.e. EMG activity) and not to sex specific differences in muscle atrophy. The overall goal of this proposed project is to determine the nature and locus of sex specific declines in neural activation of muscle brought about by muscle unloading. This will be approached by comparing unloading induced diminutions in functional neuromuscular transmission efficacy, neuromuscular junction morphology, myofiber profiles (fiber type and size) and the expression of NCAM and Synaptotagmin, two important regulatory molecules of synaptic function and structure. The project's 1st Aim will focus on examining neuromuscular remodeling in response to muscle unloading in young adult males vs. females. The 2nd Aim will examine the effect of aging on sex specific adaptations to unloading;this is vital since the aged are far more likely to suffer accidental falls and medical procedures resulting in muscle unloading. In the 3rd Aim, the causative effect of sexually dimorphic sex steroid endocrine milieus on sex specific adaptations to unloading will be evaluated. In the experiments proposed here, male and female rats will be used as subjects for the project (young adults for Aim 1, aged for Aim 2, gonadectomized young adults for Aim 3), and the hind limb suspension model of unloading will be employed. The data gathered here will provide novel insight into the newly reported and clinically important finding that male and female neuromuscular systems suffer different degrees of disturbance due to muscle unloading. By understanding the nature of this sex specific remodeling, it will be possible to optimize rehabilitative strategies following the condition of muscle unloading that occurs all too frequently in men and women of all ages.

Public Health Relevance

As a result of medical procedures and accidental falls thousands of Americans - both young and old - are subjected to muscle unloading each year eliciting impairments in neuromuscular function. Recent findings indicate that gender influences unloading induced declines in neuromuscular function. Understanding the locus and factors accounting for this gender specific remodeling is essential in order to optimize rehabilitative strategies for recovering young and aged men and women.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Academic Research Enhancement Awards (AREA) (R15)
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Skeletal Muscle and Exercise Physiology Study Section (SMEP)
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Boyce, Amanda T
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College of William and Mary
Schools of Arts and Sciences
United States
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Deschenes, Michael R; Adan, Matthew A; Kapral, Maria C et al. (2018) Neuromuscular adaptability of male and female rats to muscle unloading. J Neurosci Res 96:284-296
Deschenes, M R; Kressin, K A; Garratt, R N et al. (2016) Effects of exercise training on neuromuscular junction morphology and pre- to post-synaptic coupling in young and aged rats. Neuroscience 316:167-77
Rudolf, Rüdiger; Deschenes, Michael R; Sandri, Marco (2016) Neuromuscular junction degeneration in muscle wasting. Curr Opin Clin Nutr Metab Care 19:177-81
Deschenes, Michael R; Leathrum, Colleen M (2016) Gender-specific neuromuscular adaptations to unloading in isolated rat soleus muscles. Muscle Nerve 54:300-7
Deschenes, Michael R; Sherman, E Grace; Roby, Mackenzie A et al. (2015) Effect of resistance training on neuromuscular junctions of young and aged muscles featuring different recruitment patterns. J Neurosci Res 93:504-13
Deschenes, Michael R; Gaertner, Jennifer R; O'Reilly, Shaelyn (2013) The effects of sarcopenia on muscles with different recruitment patterns and myofiber profiles. Curr Aging Sci 6:266-72
Deschenes, Michael R; Hurst, Taylor E; Ramser, Amy E et al. (2013) Presynaptic to postsynaptic relationships of the neuromuscular junction are held constant across age and muscle fiber type. Dev Neurobiol 73:744-53
Deschenes, Michael R; McCoy, Raymond W; Mangis, Katherine A (2012) Factors relating to gender specificity of unloading-induced declines in strength. Muscle Nerve 46:210-7