Background: Beneficial effects of whole-body vibration (WBV) on brain and musculoskeletal
health in mice have been demonstrated, but underlying mechanisms remain relatively
unrevealed. WBV improves attention and memory performance in mice, putatively through
stimulation of the cholinergic system. Here, we investigated the effects of WBV on
the septo-hippocampal cholinergic system. Methods: Young C57BL/6 mice (8 weeks old)
were subjected to 10 min WBV/day (mechanical vibration: 30 Hz; ~0.1-μm peak-to-peak
displacement), 5X/week for 5 weeks. In Experiment 1, choline acetyltransferase (ChAT)-immunoreactivity
in the septum and hippocampus was analyzed either 2 or 24 h after the last WBV session.
Pseudo-WBV-treated mice (same handling procedure as WBV, but no vibrations) served
as controls. In Experiment 2, the longitudinal profile of ChAT-immunoreactivity was
analyzed in the hippocampus after 1, 2, 3, 4, or 5 weeks of WBV. In addition, synaptophysin
immunostaining was performed at either 2 and 5 weeks of WBV. Mice housed 1/cage during
the entire experiment served as controls. The balance-beam test was used to monitor
the functional impact of WBV. In Experiment 3, a Y-maze reference-memory test was
performed after 5 weeks of WBV to obtain a functional cognitive outcome measure of
WBV. Pseudo-WBV treated mice served as controls. Results: In Experiment 1, ChAT-immunoreactivity
was significantly enhanced after the last WBV session of the 5-week period. This was
found in the septum, Cornu Ammonis 1 (CA1), CA3, and dentate gyrus, and was dependent
on layer and time-point (2 or 24 h). Experiment 2 revealed that, ChAT-immunoreactivity
was lower after 2 weeks of WBV, whereas it was significantly higher after 5 weeks
(similar to in Experiment 1). Immunostaining for synaptophysin, a marker for synaptic
density, was also significantly higher after 5 weeks of WBV, but not significantly
lower after 2 weeks, as was ChAT. WBV-treated groups performed significantly better
than did controls on the balance beam from week 3 onwards. Experiment 3 showed that
WBV-treated mice had better spatial-reference memory performance in the Y-maze test
than did pseudo-WBV controls. Conclusions: Our results indicate that WBV stimulates
the septo-hippocampal cholinergic system in a gradual and dynamic way that may contribute
to improved spatial-memory performance. This finding suggests that WBV, by upregulation
of the septo-hippocampal cholinergic system, may be considered a valuable therapeutic
strategy to enhance brain functions in aging, neurodegenerative, and other brain diseases.