Neuronal-astrocytic and cytosolic-mitochondrial metabolite trafficking during brain activation, hyperammonemia and energy deprivation

A novel concept is described, according to which both neurons and astrocyte s are capable of metabolizing glucose all the way to CO2 and water, but in addition interact metabolically in a process generating glutamate from gluc ose, and subsequently, metabolizing excess glutamate to CO2 and water Hertz , L., Dringen, R., Schousboe, A., Robinson, S.R., 1999. Astrocytes: Glutama te producers for neurons (Journal of Neuroscience Research 57, 417-428). Th e proposed metabolic degradation of glucose via glutamate serves the purpos e of adjusting transmitter pools of glutamate to the demands for glutamater gic transmission, and it must account for a major fraction of glucose utili zation. Evidence in favor of this concept is presented and a multitude of i n vivo data are interpreted in the context of metabolic trafficking between neurons and astrocytes. In addition, intracellular trafficking occurs betw een cytosol and mitochondria during synthesis of transmitter glutamate, par tly explaining a robust quantitative correlation betwen glutamine synthesis , as a measure of release of transmitter glutamate, and glucose utilization , reported by several authors. Both intracellular and intercellular metabol ic trafficking may be affected during pathological conditions, as evidenced by effects of hyperammonemia (mimicking hepatic encephalopathy) and energy deprivation (mimicking stroke). It is suggested that neuronal-astrocytic i nteractions may also be impaired during degenerative dementing diseases. (C ) 2000 Published by Elsevier Science Ltd. All rights reserved.