Enhancement of neuromuscular dynamics and strength behavior using extremely low magnitude mechanical signals in mice

Abstract

Exercise in general, and mechanical signals in particular, help ameliorate the neuromuscular symptoms of aging and possibly other neurodegenerative disorders by enhancing muscle function. To better understand the salutary mechanisms of such physical stimuli, we evaluated the potential for low intensity mechanical signals to promote enhanced muscle dynamics. The effects of daily brief periods of low intensity vibration (LIV) on neuromuscular functions and behavioral correlates were assessed in mice. Physiological analysis revealed that LIV increased isometric force production in semitendinosus skeletal muscle. This effect was evident in both young and old mice. Isometric force recordings also showed that LIV reduced the fatiguing effects of intensive synaptic muscle stimulation. Furthermore, LIV increased evoked neurotransmitter release at neuromuscular synapses but had no effect on spontaneous end plate potential amplitude or frequency. In behavioral studies, LIV increased mouse grip strength and potentiated initial motor activity in a novel environment. These results provide evidence for the efficacy of LIV in producing changes in the neuromuscular system that translate into performance gains at a behavioral scale.

Keywords: Mechanical signals; Muscle strength; Neuromuscular; Quantal content; Whole body vibration.

Fig. 1

LIV increases isometric force production and enhances neuromuscular synapse-driven responsiveness in mouse skeletal muscle. Effects of 4 weeks of LIV exposure on the isometric force generation of isolated mouse semitendinosus muscle at varying frequencies of intact direct nerve stimulation from young (12 week old, n = 4, A) and aged (107 week old, n = 2–3, B) mice are summarized. LIV increased force production overall in young and old mice (p < 0.0001) for both age groups). Data represent means with standard error. For per frequency comparisons **** is p < 0.0001 and ** is p < 0.01.

Fig. 2

Isometric force recordings show fatigue of synapse-driven muscle responses is reduced and the threshold for loss of responsiveness is raised by LIV. Two representative isometric force traces from control (A) LIV exposed (B) mice are depicted. Note that control muscle responded with less peak force at stimulation rates above 10 Hz and ceases to respond significantly above 50 Hz.

Fig. 3

LIV increased evoked neurotransmitter release at neuromuscular synapses but had no effect on miniature end plate potential (MEPP) amplitude or frequency. Histograms for MEPP amplitudes (A), frequency (B), and calculated quantal content (C) measured electrophysiologically in LIV-exposed and control 12 week-old mouse semitendinosus neuromuscular junctions with accompanying example recording traces are shown. Data represent means with standard error (*p = 0.0336, n = 198–244). (D) Immunostains of neuromuscular junctions from control and LIV-treated mouse semitendinosus muscle.

Fig. 4

LIV increases mouse grip strength. Quantitation of grip strength of LIV exposed and control 12 week-old mice is shown. Data represent means with standard error (**p = 0.0097, n = 12).

Fig. 5

LIV potentiates initial motor activity in a novel environment. Plots of distance moved in an open field in 4 min bins are shown for LIV exposed and control 12 week old mice. Data represent means with standard error (*p = 0.0257, n = 12).