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Tuning the Brain: How Acoustic Energies Modulate Neural and Glial Phenotypes

Year: 2026

Type: article

Abstract: The traditional view of neuronal communication is shifting toward a mechanobiological paradigm. This review examines how mechanical energy from diverse acoustic stimuli—audible sound and whole-body or vibrotactile vibration, low-intensity pulsed ultrasound (LIPUS), low-intensity focused ultrasound (LIFU), high-intensity focused ultrasound (HIFU), and extracorporeal shockwave therapy (ESWT)—translates into biochemical signals. Evidence is stratified throughout by model system (in vitro, animal in vivo, human) and by reported exposure dose, and sensory-pathway or network-level effects of audible sound are kept distinct from direct cellular mechanotransduction. Acoustic forces are directly detected by primary mechanosensitive ion channels, such as Piezo1 and TRPV4, and experimental evidence links this mechanotransduction to neurotrophic signaling (mechanistic target of rapamycin (mTOR); p38 mitogen-activated protein kinase (MAPK); brain-derived neurotrophic factor (BDNF)) that supports neurite outgrowth and structural repair, whereas a continuous signaling axis running from the cytoskeleton through the linker of nucleoskeleton and cytoskeleton (LINC) complex to epigenetic regulation remains a mechanistic hypothesis that has not been demonstrated in any acoustically stimulated neural cell. Furthermore, glial cells act as active mechanosensors, and emerging evidence suggests that acoustic stimulation can promote microglial polarization toward neuroprotective M2 phenotypes and may support Schwann cell-mediated peripheral nerve regeneration. We discuss the emerging concept of “acoustic pharmacology,” in which specific waveforms and frequencies dictate distinct therapeutic outcomes. From targeted amyloid clearance in Alzheimer’s disease to the non-invasive neural circuit control offered by sonogenetics, acoustic stimulation is a tunable but still predominantly preclinical frontier in regenerative medicine and neuromodulation: of the 144 sources cited here, seven report human studies, and the only randomized, sham-controlled evidence with a clinical endpoint concerns ablative high-intensity focused ultrasound; for the non-ablative neuromodulatory, neuroprotective, and regenerative regimes that are the subject of this review, no such trial is present in this evidence base.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms27219481