Dataset Information

Muscle strength and size are associated with motor unit connectivity in aged mice.

ABSTRACT: In older adults, the loss of muscle strength (dynapenia) and the loss of muscle mass (sarcopenia) are important contributors to the loss of physical function. We sought to investigate dynapenia, sarcopenia, and the loss of motor unit function in aging mice. C57BL/6J mice were analyzed with cross-sectional (males: 3 vs. 27 months; males and females: 8 vs. 12 vs. 20 months) and longitudinal studies (males: 10-25 months) using in vivo electrophysiological measures of motor unit connectivity (triceps surae compound muscle action potential and motor unit number estimation), in vivo measures of plantar flexion torque, magnetic resonance imaging of hind limb muscle volume, and grip strength. Compound muscle action potential amplitude, motor unit number estimation, and plantar flexion torque were decreased at 20 months. In contrast, grip strength was reduced at 24 months. Motor unit number estimates correlated with muscle torque and hind limb muscle volume. Our results demonstrate that the loss of motor unit connectivity is an early finding in aging male and female mice and that muscle size and contractility are both associated with motor unit number.

SUBMITTER: Sheth KA

PROVIDER: S-EPMC5981861 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Muscle strength and size are associated with motor unit connectivity in aged mice.

Sheth Kajri A KA Iyer Chitra C CC Wier Christopher G CG Crum Alexander E AE Bratasz Anna A Kolb Stephen J SJ Clark Brian C BC Burghes Arthur H M AHM Arnold W David WD

Neurobiology of aging 20180323

In older adults, the loss of muscle strength (dynapenia) and the loss of muscle mass (sarcopenia) are important contributors to the loss of physical function. We sought to investigate dynapenia, sarcopenia, and the loss of motor unit function in aging mice. C57BL/6J mice were analyzed with cross-sectional (males: 3 vs. 27 months; males and females: 8 vs. 12 vs. 20 months) and longitudinal studies (males: 10-25 months) using in vivo electrophysiological measures of motor unit connectivity (tricep ...[more]

PMID: 29656012

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Project description:Sarcopenia is a progressive and generalized disease, more common in older adults, which manifests as a loss of muscle strength and mass. The pathophysiology of sarcopenia is still poorly understood with many mechanisms suggested. Age associated changes to the neuromuscular architecture, including motor units and their constituent muscle fibres, represent one such mechanism. Electromyography can be used to distinguish between different myopathies and produce counts of motor units. Evidence from electromyography studies suggests that with age, there is a loss of motor units, increases to the sizes of remaining units, and changes to their activity patterns. However, electromyography is invasive, can be uncomfortable, does not reveal the exact spatial position of motor units within muscle and is difficult to perform in deep muscles. We present a novel diffusion-weighted magnetic resonance imaging technique called 'motor unit magnetic resonance imaging (MUMRI)'. MUMRI aims to improve our understanding of the changes to the neuromuscular system associated with ageing, sarcopenia and other neuromuscular diseases. To date, we have demonstrated that MUMRI can be used to detect statistically significant differences in fasciculation rate of motor units between (n = 4) patients with amyotrophic lateral sclerosis (mean age ± SD: 53 ± 15) and a group of (n = 4) healthy controls (38 ± 7). Patients had significantly higher rates of fasciculation compared with healthy controls (mean = 99.1/min, range = 25.7-161.0 in patients vs. 7.7/min, range = 4.3-9.7 in controls; P < 0.05. MUMRI has detected differences in size, shape, and distribution of single human motor units between (n = 5) young healthy volunteers (29 ± 2.2) and (n = 5) healthy older volunteers (65.6 ± 14.8). The maximum size of motor unit territories in the older group was 12.4 ± 3.3 mm and 9.7 ± 2.7 mm in the young group; P < 0.05. MUMRI is an entirely non-invasive tool, which can be used to detect physiological and pathological changes to motor units in neuromuscular diseases. MUMRI also has the potential to be used as an intermediate outcome measure in sarcopenia trials.

Project description:Localised signal voids in diffusion-weighted (DW) images of skeletal muscle have been postulated to occur as a result of muscle fibre contraction and relaxation. We investigated the contrast mechanism of these signal voids using a combination of modelling and experimental measurements by employing DW and phase contrast (PC) imaging sequences. The DW signal and PC signal were simulated for each time point of a theoretical muscle twitch. The model incorporated compaction (simulating actively contracting muscle fibres) and translation (simulating passively moving surrounding fibres). The model suggested that the DW signal depended on contraction time and compaction whereas the PC signal depended on contraction time, compaction and translation. In a retrospective study, we tested this model with subgroup analyses on 10 healthy participants. Electrical nerve stimulation was used to generate muscle twitches in lower leg muscles; the resulting force was measured using an MR-compatible force transducer. At current levels causing a visible muscle twitch (~13 mA), the width of the first signal drop in the DW signal (mean ± SD: 103 ± 20 ms) was comparable with the force contraction time (93 ± 34 ms; intraclass correlation coefficient [ICC] = 0.717, P = .010). At current levels activating single motor units (~9 mA), the contraction time determined from the DW signal was 75 ± 13 ms and comparable with the PC contraction time (81 ± 15 ms; ICC = 0.925, P = .001). The maximum positive velocity was 0.55 ± 0.26 cm/s and the displacement was 0.20 ± 0.10 mm. Voxel-wise analysis revealed localised DW changes occurring together with more widespread phase changes. In conclusion, local signal attenuations in DW images following muscle fibre activation are primarily caused by compaction. The PC sequence also detects translating muscle tissue being passively pulled. The magnitude of the changes in DW and PC images depends on the twitch's contractile properties and percentage contraction. DW imaging and PC imaging can therefore measure twitch profiles of skeletal muscle fibres.

Dataset Information

Muscle strength and size are associated with motor unit connectivity in aged mice.

Publications

Muscle strength and size are associated with motor unit connectivity in aged mice.

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