The vestibular system is critical for the changes in muscle and bone induced by hypergravity in mice

Abstract

Gravity changes concurrently affect muscle and bone as well as induce alterations in vestibular signals. However, the role of vestibular signals in the changes in muscle and bone induced by gravity changes remains unknown. We therefore investigated the effects of vestibular lesions (VL) on the changes in muscle and bone induced by 3 g hypergravity for 4 weeks in C57BL/6J mice. Quantitative computed tomography analysis revealed that hypergravity increased muscle mass surrounding the tibia and trabecular bone mineral content, adjusting for body weight in mice. Hypergravity did not affect cortical bone and fat masses surrounding the tibia. Vestibular lesions blunted the increases in muscle and bone masses induced by hypergravity. Histological analysis showed that hypergravity elevated the cross‐sectional area of myofiber in the soleus muscle. The mRNA levels of myogenic genes such as MyoD, Myf6, and myogenin in the soleus muscle were elevated in mice exposed to hypergravity. Vestibular lesions attenuated myofiber size and the mRNA levels of myogenic differentiation markers enhanced by hypergravity in the soleus muscle. Propranolol, a β‐blocker, antagonized the changes in muscle induced by hypergravity. In conclusion, this study is the first to demonstrate that gravity changes affect muscle and bone through vestibular signals and subsequent sympathetic outflow in mice.

Roles of the vestibular system in obesity and impaired glucose metabolism in high-fat diet-fed mice

“…Previous studies revealed that VL reduced BMD through the activation of the sympathetic nervous system in rodents [5,34]. Moreover, we reported that an adrenergic β-blocker antagonized the effects of hypergravity on skeletal muscle masses through the vestibular system in mice [8]. These findings suggest that the sympathetic nervous system is involved in the effects of the vestibular system on the cardiovascular system, bone metabolism, and skeletal muscle.…”

“…Luxa et al reported that labyrinthectomy increased myofiber remodeling in the soleus muscle of mice [6]. We recently revealed that gravity changes affect muscle and bone through the vestibular system in mice [7,8]. Collectively, these findings suggest that the vestibular system regulates the musculoskeletal system partly through the sympathetic nervous system.…”

“…Male C57BL/6J mice were divided into 4 groups: ND/Control (n = 8), ND/propranolol (n = 8), HSHFD/Control (n = 8), and HSHFD/propranolol (n = 8). Propranolol (Sigma, St. Louis, MO, USA) was administered to 9-week-old mice via drinking water at 0.5 g/l for 8 weeks, as described previously [8].…”

Understanding vestibular-related physiological functions could provide clues on adapting to a new gravitational environment

“…Therefore, we speculated that gravity change influences muscle-bone interactions by affecting muscle-derived factors (myokines) that link muscle to bone, which might have a partial involvement in microgravity-induced changes in muscle and bones. We investigated the hypergravity effects on muscles and bones in mice using the gondola-type centrifuge in a 3g environment with or without VL [13]. We found that a 4-week exposure to hypergravity in a 3g environment increased the anti-gravity muscle weight and fiber size, as well as the expression of muscle differentiation genes, including MyoD.…”

“…The vestibular organ detects acceleration changes and converts them into neural signals, which are sent to the central nervous system to reflexively regulate physiological functions, including body stability (vestibulo-spinal reflex) [1], ocular movements (vestibulo-ocular reflex) [2,3], sympathetic nerve activity (vestibulo-sympathetic reflex) [4][5][6], arterial pressure (vestibulo-cardiovascular reflex), food intake [7], and body temperature [5,[8][9][10]. There have been recent reports on vestibular-related muscle and bone metabolism [11][12][13][14] and increasing attention on the various vestibular system functions. The vestibular system is known to be highly plastic, i.e., its sensitivity might be altered upon exposure to a different gravitational environment.…”