Astrocyte sensitivity to glymphatic shear stress is amplified by albumin and mediated by the interaction of sphingosine 1 phosphate with Piezo1

Abstract

Astrocyte endfeet enwrap brain vasculature, forming a boundary for perivascular glymphatic flow of fluid and solutes along and across the astrocyte endfeet into the brain parenchyma. To determine whether astrocytes may sense and respond to the shear forces generated by glymphatic flow, we examined intracellular calcium (Ca2+) changes evoked in astrocytes to brief fluid flow applied in calibrated microfluidic chambers. Shear stresses View larger version (21K): org.highwire.dtl.DTLVardef@17086e6org.highwire.dtl.DTLVardef@a89f32org.highwire.dtl.DTLVardef@6baed5org.highwire.dtl.DTLVardef@1a32f80_HPS_FORMAT_FIGEXP M_FIG C_FIG Astrocyte endfoot responds to glymphatic shear stress when albumin is present. Mechanism involves sphingosine-1-phosphate (S1P) binding to its receptor (S1PR), activating phospholipase C (PLC) and thereby sensitizing the response of Piezo1 to flow. Ca2+ influx triggers Ca2+ release from intracellular stores and further downstream signaling, thereby modulating parenchymal perfusion. Illustration created using BioRender.com