Metabolic signaling in the brain and the role of astrocytes in control of glutamate and GABA neurotransmission.

Neurotransmission mediated by the two amino acids glutamate and GABA is based on recycling of the two signaling molecules between the presynaptic nerve endings and the surrounding astrocytes. During the recycling process, a fraction of the transmitter pool is lost since both transmitters undergo oxidative metabolism. This loss must be replenished by de novo synthesis which involves the action of pyruvate carboxylase, aminotransferases, glutamate dehydrogenase and glutamine synthetase. Among these enzymes, pyruvate carboxylase and glutamine synthetase are selectively expressed in astrocytes and thus these cells are obligatory partners in synaptic replenishment of both glutamate and GABA. The cycling processes also involve transporters for glutamate, GABA and glutamine and the operation of these transporters is discussed. Additionally, astrocytes appear to be essential for production of the neuromodulators, citrate, glycine and d-serine, aspects that will be briefly discussed.