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 simple 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. Particularly, in the honeybee retina, photoreceptor-neurons consume alanine supplied by glial cells and exogenous proline. NH4+ and glutamate are transported into glia by functional plasma membrane transport systems. During 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 biochemistry showed that this is due to activation of glycolysis in glial cells by the direct action of NH4+ and of glutamate, probably on the enzymatic reactions controlled by phosphofructokinase alanine aminotransferase and glutamate dehydrogenase. This activation leads to a massive increase in the production and release of alanine by glia. This constitutes an intracellular signal and it depends upon the rate of conversion of NH4+ and of glutamate to alanine and alpha-ketoglutarate, respectively, in the glial cells. Alanine and alpha-ketoglutarate are released extracellularly and then taken up by neurons where they contribute to the maintenance of the mitochondrial redox potential. This signaling raises the novel hypothesis of a tight regulation of the nutritive function of glia.
Tsacopoulos
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M
Department of Physiology, University of Geneva Medical School, Switzerland.
Poitry-Yamate
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Poitry
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Perrottet
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Veuthey
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D000409:Alanine / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001516:Bees; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008954:Models, Biological; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D017956:Photoreceptor Cells, Invertebrate / Q000502:physiology*; D011392:Proline / Q000378:metabolism; D012160:Retina / Q000502:physiology; D015398:Signal Transduction
D009243:NAD; D018698:Glutamic Acid; D009249:NADP; D000641:Ammonia; D011392:Proline; D005947:Glucose; D000409:Alanine