Dose-Response Effect of Vibratory Stimulus on Synaptic and Muscle Plasticity in a Middle-Aged Murine Model

Abstract

Whole body vibration plays a central role in many work categories and can represent a health risk to the musculoskeletal system and peripheral nervous system. However, studies in animal and human models have shown that vibratory training, experimentally and/or therapeutically induced, can exert beneficial effects on the whole body, as well as improve brain functioning and reduce cognitive decline related to the aging process. Since the effects of vibratory training depend on several factors, such as vibration frequency and vibration exposure time, in this work, we investigated whether the application of three different vibratory protocols could modulate synaptic and muscle plasticity in a middle-aged murine model, counteracting the onset of early symptoms linked to the aging process. To this end, we performed in vitro electrophysiological recordings of the field potential in the CA1 region of mouse hippocampal slices, as well as histomorphometric and ultrastructural analysis of muscle tissue by optic and transmission electron microscopy, respectively. Our results showed that protocols characterized by a low vibration frequency and/or a longer recovery time exert positive effects at both hippocampal and muscular level, and that these effects improve significantly by varying both parameters, with an action comparable with a dose-response effect. Thus, we suggested that vibratory training may be an effective strategy to counteract cognitive impairment, which is already present in the early stages of the aging process, and the onset of sarcopenia, which is closely related to a sedentary lifestyle. Future studies are needed to understand the underlying molecular mechanisms and to determine an optimal vibratory training protocol.

Keywords: hippocampus; mechanical vibration; muscle plasticity; synaptic plasticity; whole body vibration.

FIGURE 1

Synaptic plasticity in CA1 hippocampal subfield of old mice.% population spike (PS) amplitude as a function of time after HFS, applied at time t = 15 (arrow), is shown in CTRL WBV (black line, n = 7), in CTRL SED (gray line, n = 7), in A-TRAINED (blue line, n = 7), in B-TRAINED (red line, n = 8), and in C-TRAINED (green line, n = 9) mice slices. The insert shows representative recordings obtained from slices of each experimental group; the curves of each group refer to population spike at times 5, 15, 45, and 65 min.

FIGURE 2

Evaluation of muscle fiber diameter following whole body vibration (WBV) training by histomorphometric analysis. The upper four panels show a representative section of muscle tissue from each experimental group (scale bar, 50 μm). The lower panel shows the mean value of the muscle fibers diameter in CTRL WBV (black bar, n = 150), in CTRL SED (gray bar, n = 150), in A-TRAINED (blue bar, n = 150), in B-TRAINED (red bar, n = 150), and in C-TRAINED (green bar, n = 150) groups. Note that a significant increase in muscle fiber diameter was found in the trained groups compared with the control groups (CTRL WBV and CTRL SED vs A-TRAINED, **p < 0.01; CTRL WBV and CTRL SED vs B-TRAINED, ***p < 0.001; and CTRL WBV and CTRL SED vs C-TRAINED, ****p < 0.0001).

FIGURE 3

Electron microscopy analysis of the muscle tissues following WBV training. (A) Image displays degenerated sarcomeric network of CTRL groups, (B) with numerous lipid droplets and increase in atrophic fibers. (C) Electron micrograph shows several lipid droplets (arrowheads) next to mitochondria. (D) Muscle tissue of the A-TRAINED group was characterized by altered sarcomeric structures, (E) abundant inter-fiber fibrosis and presence of atrophic muscle fibers. (F) Enlargement of panel (E) highlights the fibrotic tissue (asterisks). (G) Image shows an improvement in muscle tissue fibers in the B-TRAINED group, (H) with the presence of normal fibers alternating with slightly atrophic ones. (I) Image displays a sarcomeric ultrastructure in a muscle of B-TRAINED mouse. (J) Muscle tissue of the C-TRAINED group shows normal sarcomeric structures, (K) with numerous and well-preserved mitochondria. (L) Enlargement of panel (K) highlights well-preserved dark mitochondria (asterisks) in a muscle of C-TRAINED mouse. Scale bar, 5, 2, and 0.5 μm.