Glia in brain energy metabolism: A perspective.

Early views of glia as relatively inert, housekeeping cells have evolved, and glia are now recognized as dynamic cells that not only respond to neuronal activity but also sense metabolic changes and regulate neuronal metabolism. This evolution has been aided in part by technical advances permitting progressively better spatial and temporal resolution. Recent advances in cell-type specific genetic manipulation and sub-cellular metabolic probes promise to further this evolution by enabling study of metabolic interactions between intertwined fine neuronal and glial processes in vivo. Views of glia in disease processes have also evolved. Long considered purely reactive, glia and particularly microglia are now seen to play active roles in both promoting and limiting brain injury. At the same time, established concepts of glial energetics are now being linked to areas such as learning and neural network function, topics previously considered far removed from glial biology.

Extracellular conversion of guanine-based purines to guanosine specifically enhances astrocyte glutamate uptake.

Guanosine (GUO) has been shown to stimulate glutamate uptake in primary astrocyte cultures. The purpose of this study was to determine the effect and specificity of guanine- or adenine-based purines on glutamate and GABA uptake in cultured astrocytes. Stimulatory effect on glutamate uptake was observed with GUO, GMP or GTP. Simultaneous exposure with these guanine-based purines did not show an additive effect. We also investigated a possible interconversion of guanine-based purines during incubation time. Action by GTP was excluded since the hydrolysis resistant GTP analog, GMP-PNP did not stimulate glutamate uptake. Addition of an ecto-5'-nucleotidase inhibitor abolished GMP-stimulatory effect on glutamate uptake, without affecting GUO action. Taken together, these results suggest that GUO is the guanine-based purines responsible for glutamate uptake activation. In addition, the stimulatory effect on glutamate uptake was not observed with adenine-based purines. Moreover, GABA uptake was not activated by GUO. These results point to specificity in the interaction between GUO and the astrocyte glutamate uptake system.