Glutamate Homeostasis as a Regulator of Neurotransmitter Recycling and Synaptic Function

• Published in: Homeostatic Control of Brain Function
• Main Authors: Ellen Kelly, Mary, Coulter, Douglas A.
• Format: Book Chapter
• Language: English
• Published: Oxford University Press 01.11.2015
• ISBN: 9780199322299; 0199322295
• DOI: 10.1093/med/9780199322299.003.0003

Astrocytes play a critical role in regulation of extracellular glutamate levels in the central nervous system, with estimates that 80–90% of extracellular glutamate uptake in brain is through astrocytic glutamate transporters. This glial uptake mechanism is important both for normal recycling of inhibitory and excitatory neurotransmitter, and also in regulation of potentially toxic accumulations of extracellular glutamate. In this chapter I will summarize the glutamateglutamine cycle, which is critical in the resupply of neurotransmitter. This cycle involves astroglial uptake of glutamate, transformation of glutamate to glutamine by the astrocytic enzyme glutamine synthetase (GS), and shuttling of glutamine back to excitatory and inhibitory neurons via specialized transporters. Once in neurons, glutamine is enzymatically converted back to glutamate, which is utilized for synaptic transmission, either directly, or following decarboxylation to GABA. In addition, I will discuss the fact that many neurologic and psychiatric conditions, particularly epilepsy, are accompanied by the development of reactive gliosis, a pathology characterized by anatomical and biochemical plasticity in astrocytes, which is accompanied by a downregulation of several of the important regulators of the glutamine–glutamate cycle, including GS, and possibly also glutamate transporters. Finally, I will summarize recent evidence that this downregulation in function of the glutamate glutamine cycle may contribute to the aberrant excitability characterizing epilepsy.