Energy substrates to support glutamatergic and GABAergic synaptic function: role of glycogen, glucose and lactate

Maintenance of glutamatergic and GABAergic activity requires a continuous supply of energy since the exocytotic processes as well as high affinity glutamate and GABA uptake and subsequent metabolism of glutamate to glutamine are energy demanding processes. The main energy substrate for the brain under normal conditions is glucose but at the cellular level, i.e., neurons and astrocytes, lactate may play an important role as well. In addition to this the possibility exists that glycogen, which functions as a glucose storage molecule and which is only present in astrocytes, could play a role not only during aglycemia but also during normoglycemia. These issues are discussed and it is concluded that both glucose and lactate are of importance for the maintenance of normal glutamatergic and GABAergic activity. However, with regard to maintenance of an adequate capacity for glutamate transport, it appears that glucose metabolism via the glycolytic pathway plays a fundamental role. Additionally, evidence is presented to support the notion that glycogen turnover may play an important role in this context. Moreover, it should be noted that the amino acid neurotransmitters can be used as metabolic substrates. This requires pyruvate recycling, a process that is discussed as well.