Astrocytic Control of Biosynthesis and Turnover of the Neurotransmitters Glutamate and GABA
Open Access
- 1 January 2013
- journal article
- Published by Frontiers Media SA in Frontiers in Endocrinology
- Vol. 4, 102
- https://doi.org/10.3389/fendo.2013.00102
Abstract
Glutamate and GABA are the quantitatively major neurotransmitters in the brain mediating excitatory and inhibitory signaling, respectively. These amino acids are metabolically interrelated and at the same time they are tightly coupled to the intermediary metabolism including energy homeostasis. Astrocytes play a pivotal role in the maintenance of the neurotransmitter pools of glutamate and GABA since only these cells express pyruvate carboxylase, the enzyme required for de novo synthesis of the two amino acids. Such de novo synthesis is obligatory to compensate for catabolism of glutamate and GABA related to oxidative metabolism when the amino acids are used as energy substrates. This, in turn, is influenced by the extent to which the cycling of the amino acids between neurons and astrocytes may occur. This cycling is brought about by the glutamate/GABA – glutamine cycle the operation of which involves the enzymes glutamine synthetase (GS) and phosphate-activated glutaminase together with the plasma membrane transporters for glutamate, GABA, and glutamine. The distribution of these proteins between neurons and astrocytes determines the efficacy of the cycle and it is of particular importance that GS is exclusively expressed in astrocytes. It should be kept in mind that the operation of the cycle is associated with movement of ammonia nitrogen between the two cell types and different mechanisms which can mediate this have been proposed. This review is intended to delineate the above mentioned processes and to discuss quantitatively their relative importance in the homeostatic mechanisms responsible for the maintenance of optimal conditions for the respective neurotransmission processes to operate.Keywords
This publication has 94 references indexed in Scilit:
- The Glutamate–Glutamine (GABA) Cycle: Importance of Late Postnatal Development and Potential Reciprocal Interactions between Biosynthesis and DegradationFrontiers in Endocrinology, 2013
- The Role of Glutamine Synthetase and Glutamate Dehydrogenase in Cerebral Ammonia HomeostasisNeurochemical Research, 2012
- Aspects of Astrocyte Energy Metabolism, Amino Acid Neurotransmitter Homoeostasis and Metabolic CompartmentationASN Neuro, 2012
- Novel Model of Neuronal Bioenergetics: Postsynaptic Utilization of Glucose but not Lactate Correlates Positively with Ca2+ Signalling in Cultured Mouse Glutamatergic NeuronsASN Neuro, 2012
- Deletion of the betaine–GABA transporter (BGT1; slc6a12) gene does not affect seizure thresholds of adult miceEpilepsy Research, 2011
- Mechanism of Ca2+/calmodulin-dependent kinase II regulation of AMPA receptor gatingNature Neuroscience, 2011
- Glycogenolysis in Astrocytes Supports Blood-Borne Glucose Channeling Not Glycogen-Derived Lactate Shuttling to Neurons: Evidence from Mathematical ModelingJournal of Cerebral Blood Flow & Metabolism, 2010
- Knockout of GAD65 has Major Impact on Synaptic GABA Synthesized from Astrocyte-Derived GlutamineJournal of Cerebral Blood Flow & Metabolism, 2010
- A quantitative assessment of glutamate uptake into hippocampal synaptic terminals and astrocytes: New insights into a neuronal role for excitatory amino acid transporter 2 (EAAT2)Neuroscience, 2008
- Supply and Demand in Cerebral Energy Metabolism: The Role of Nutrient TransportersJournal of Cerebral Blood Flow & Metabolism, 2007