Glutamate Metabolism

The majority of energy consumed by the brain is used to maintain membrane potentials of neurons after action potentials are fired. Glutamate, the main neurotransmitter in the central nervous system (CNS), is responsible for a large percentage of this energy expenditure. Accumulation of glutamate, however, can be toxic to neurons and, therefore, must be tightly regulated. The brain uses a combination of the blood–brain barrier, powerful glial transporters, metabolic enzymes, and glutamate cycling to maintain low extracellular levels of glutamate. These protective mechanisms, however, can become dysregulated in epilepsy. Both human and animal studies have shown that glutamate uptake into astrocytes is hindered, the metabolic processing of glutamate is slowed, and the cycling of glutamate to glutamine is downregulated in epileptic tissue. Future studies should be aimed at furthering our understanding of the functional consequences of these changes.