THE NUTRITIVE FUNCTION OF GLIA IS REGULATED BY SIGNALS RELEASED BY NEURONS

The idea of a metabolic coupling between neurons and astrocytes in the brain has been entertained for about 100 years. The use recently of s imple and well-compartmentalized nervous systems, such as the honeybee retina or purified preparations of neurons and glia, provided strong support for a nutritive function of glial cells: glial cells transform glucose to a fuel substrate taken up and used by neurons. Particularl y, in the honeybee retina, photoreceptor-neurons consume alanine suppl ied by glial cells and exogenous proline. NH4+ and glutamate are trans ported into glia by functional plasma membrane transport systems. Duri ng increased activity a transient rise in the intraglial concentration of NH4+ or of glutamate causes a net increase in the level of reduced nicotinamide adenine dinucleotides [NAD(P)H]. Quantitative biochemist ry showed that this is due to activation of glycolysis in glial cells by the direct action of NH4+ and of glutamate, probably on the enzymat ic reactions controlled by phosphofructokinase alanine aminotransferas e and glutamate dehydrogenase. This activation leads to a massive incr ease in the production and release of alanine by glia. This constitute s an intracellular signal and it depends upon the rate of conversion o f NH4+ and of glutamate to alanine and alpha-ketoglutarate, respective ly, in the glial cells. Alanine and alpha-ketoglutarate are released e xtracellularly and then taken up by neurons where they contribute to t he maintenance of the mitochondrial redox potential. This signaling ra ises the novel hypothesis of a tight regulation of the nutritive funct ion of glia. (C) 1997 Wiley-Liss, Inc.