Metabolic trafficking through astrocytic gap junctions

Astrocytes are interposed between the pericapillary space and neuronal membranes. Consequently, they may represent an important intermediary element between the source of energetic substrates and the main site of energy-consuming elements, respectively, the blood circulation and the neurons. A typical feature of astrocytes is the connections they establish between each other by specialized membrane structures, defined as gap junctions. These intercellular junctions allow direct cell-to-cell exchanges of ions and small molecules, including several compounds involved in major metabolic pathways occurring in astrocytes. The permeability of astrocytes gap junction channels is controlled by several endogenous compounds released by astrocytes themselves or by other brain cell types, including neurons and endothelial cells. In primary cultures of astrocytes, the intercellular diffusion, the utilization and the uptake of glucose and derivates are modified when gap junctional permeability is inhibited by uncoupling agents. Altogether these observations indicate that intercellular pathways constituted by groups of coupled astrocytes could participate to the metabolism and the distribution of energetic substrates throughout the brain.