Rho‐kinase inhibition by fasudil modulates pre‐synaptic vesicle dynamics

The Rho kinase (ROCK) signaling pathway is an attractive therapeutic target in neurodegeneration since it has been linked to the prevention of neuronal death and neurite regeneration. isoquinoline derivative fasudil a potent ROCK inhibitor, which already approved for chronic clinical treatment humans. However, effects treatments on function are still unknown. We analyzed here primary rat hippocampal cultures. Neurons were stimulated with 20 Hz field stimulation we investigated pre-synaptic mechanisms parameters regulating synaptic transmission after by super resolution emission depletion (STED) microscopy, live-cell fluorescence imaging, western blotting. Fasudil did not affect basic or amount several proteins, but altered dynamics vesicles. reduced proportion actively recycling vesicles, shortened vesicle lifetime, resulting overall reduction response upon stimulation. conclude that does alter structure, accelerates turnover, decreases number released This broadens known spectrum this drug, suggests new potential uses.