INTRODUCTION: Piezos are mechanosensitive transmembrane ion channels that convert mechanical stimuli into intracellular signals. In humans, Piezo1 and Piezo2 are primarily expressed in the cerebral cortex and white matter, respectively. Recent studies implicate Piezo channels in oligodendrocyte biology. Inhibition of Piezos using siRNAs or antagonists (Gd³⁺, GsMTx4) shows neuroprotective effects and prevents chemically induced demyelination, while activation with Yoda-1 promotes demyelination and neuronal damage. Disruption of oligodendrocyte and OPC function in the CNS contributes to neurodegenerative diseases like AD, MS, PD, and HD. White matter alterations—particularly in the parahippocampal region and hippocampus—are linked to cognitive decline and memory deficits in AD highlighting the role of WM pathology and glial dysfunction in neurodegeneration.

AIM(S): to determine the expression profile of Piezo ion channels in OPCs throughout the stages of differentiation and myelination Examine do mechanical stimuli activate Piezo channels in OPCs and what downstream signaling cascades are engaged as a result How modulation of Piezo activity affects the morphological and functional development of myelinating cells

METHOD(S): Primary OPCs are harvested from the cerebral cortices of postnatal day 4–7 C57BL/6 mouse pups. Cells are dissociated enzymatically and purified via magnetic-activated cell sorting (MACS) using anti-PDGFRα-coated beads

RESULTS: Recent studies indicate that Piezo1 is expressed in OPCs and plays a complex role in myelination. Activation of Piezo1 with Yoda1 shown to induce demyelination and neuronal damage in ex vivo models, suggesting that overactivation of Piezo1 neg impacts myelination. Inhibition of Piezo1 using GsMTx4 attenuates demyelination and promotes remyelination in ex vivo and in vivo models, indicating a protective effect against myelin loss

CONCLUSIONS: Our findings support a growing body of evidence that mechanosensitive Piezo channels are active participants in the regulation of myelination