摘要：SummaryMechanical forces are known to be involved in various biological processes. However, it remains unclear whether brain functions are mechanically regulated under physiological conditions. Here, we demonstrate that treadmill running and passive head motion (PHM), both of which produce mechanical impact on the head, have similar effects on the hallucinogenic 5-hydroxytryptamine (5-HT) receptor subtype 2A (5-HT2A) signaling in the prefrontal cortex (PFC) of rodents. PHM generates interstitial fluid movement that is estimated to exert shear stress of a few pascals on cells in the PFC. Fluid shear stress of a relevant magnitude on cultured neuronal cells induces ligand-independent internalization of 5-HT2Areceptor, which is observed in mouse PFC neurons after treadmill running or PHM. Furthermore, inhibition of interstitial fluid movement by introducing polyethylene glycol hydrogel eliminates the effect of PHM on 5-HT2Areceptor signaling in the PFC. Our findings indicate that neuronal cell function can be physiologically regulated by mechanical forces in the brain.Graphical AbstractDisplay OmittedHighlights•Mechanical forces regulate brain functions under physiological conditions•Intracerebral interstitial fluid has mechanical roles in regulating brain functions•Mechanical impact on the head mediates effects of exercise on the brain•Fluid shear stress physiologically modulates signaling in nervous cellsBiological Sciences; Neuroscience; Molecular Neuroscience; Cellular Neuroscience
