Neural Progenitor Cells Regulate Capillary Blood Flow in the Postnatal Subventricular Zone

Abstract

In the postnatal subventricular zone (SVZ), S phase entry of neural progenitor cells (NPCs) correlates with a local increase in blood flow. However, the cellular mechanism controlling this hemodynamic response remains unknown. We show that a subpopulation of SVZ cells, astrocyte-like cells or B-cells, sends projections ensheathing pericytes on SVZ capillaries in young mice. We examined whether calcium increases in pericytes or B-cells led to a vascular response in acute slices using the P2Y_2/4 receptor (P2Y_2/4R) agonist UTP, electrical stimulation, or transgenic mice expressing exogenous Gq-coupled receptors (MrgA1) in B-cells. UTP increased calcium in pericytes leading to capillary constrictions. Electrical stimulation induced calcium propagation in SVZ cells followed by capillary constrictions involving purinergic receptors. In transgenic mice, selective calcium increases in B-cells induced P2Y_2/4R-dependent capillary constrictions, suggesting that B-cells release ATP activating purinergic receptors on pericytes. Interestingly, in the presence of a P2Y_2/4R blocker, dilation was observed. Intraventricular UTP injection transiently decreased blood flow monitored in vivo using laser Doppler flowmetry. Using neonatal electroporation, we expressed MrgA1 in slow cycling radial glia-derived B1 cells, i.e., NPCs. Intraventricular injection of an MrgA1 ligand increased blood flow in the SVZ. Thus, upon intracellular calcium increases B-cells/NPCs release ATP and vasodilating factors that activate purinergic receptors on pericytes triggering a vascular response and blood flow increase in vivo. Considering that NPCs receive signals from other SVZ cells, these findings further suggest that NPCs act as transducers of neurometabolic coupling in the SVZ.