Brain pericytes increase sodium-dependent glutamate uptake in astrocytes.

Brain pericytes located in the brain capillaries are surrounded by astrocytic endfeets where glutamate transporters express. The uptake of glutamate, an excitatory neurotransmitter, in astrocytes is mediated by sodium-dependent glutamate transporter including glial glutamate transporter (GLT)-1 to regulate the extracellular glutamate concentration. However, little is known about the role of pericyte on the glutamate homeostasis maintained by astrocyte. To evaluate an effect of the pericytes on glutamate uptake by astrocytes, we prepared human brain-derived pericyte and astrocyte coculture system. The uptake of [3H]-L-glutamate by astrocytes was expressed as the cell/medium ratio. The uptake levels of glutamate in astrocytes cocultured with pericytes were significantly higher than those in astrocyte monoculture. Elevated glutamate uptake in the astrocytes cocultured with pericytes was not observed under the condition with Na+-free medium and blocked by the selective GLT-1 inhibitor dihydrokainic acid. These data showed that pericytes increase glutamate uptake in astrocytes by upregulating transporter activity. Based on these findings, pericytes may facilitate glutamate clearance in brain pericapillary location by increasing the astrocytic glutamate uptake through sodium-dependent transporter including GLT-1.