Background: Sound is a kind of mechanical stimulus and has various effects on the growth and metabolism of plants and animal cells. In previous studies, it was confirmed that sound stimulation promotes the neurodifferentiation process of mesenchymal stem cells. In this study, we examined the effect of sound on the maturation of neuroblastoma cells, SH-SY5Y cells, and investigated its effect on an ischemic mouse stroke model. In the in vitro study, SH-SY5Y cells were exposed to the sound for 3 days and then performed rt-PCR, FACS, and western blot for analysis. In the in vivo study, mesenchymal stem cells were injected into the injured area, and then rats were exposed to sound for 4 weeks. Then, immunohistochemical staining and western blotting were performed.

Results: Sound upregulated the expression of presynaptic proteins synaptophysin and postsynaptic density protein 95, as well as neuronal-related proteins such as NFL, Tau, and MAP2. T-type calcium channels such as CACNA1G and CACNA1I were also induced by sound. In an experiment using the brain of ischemic mice, the expression of proteins involved in neuronal differentiation such as MAP2, NF200, and S100 was increased, while the inflammation-related proteins IFNγ, MMP9, and TNFα were decreased. In this neuronal differentiation process, both ERK and CREB, which are proteins involved in the initial signal transduction process, were activated.

Conclusions: Our study demonstrates that sound, with the advantage of being non-invasive and easy to use, is an effective stimulus that induces neural differentiation and maturation on animal cells.