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Nutrients, Neurotransmitters and Brain Energetics

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Front. Neurosci. | doi: 10.3389/fnins.2018.01035

GLYCOLYSIS-DERIVED COMPOUNDS FROM ASTROCYTES THAT MODULATE SYNAPTIC COMMUNICATION

  • 1Universidade Federal do Rio Grande do Sul (UFRGS), Brazil

Based on the concept of the tripartite synapse, we reviewed the role of glucose-derived compounds from glycolytic pathways in astroglial cells. Glucose provides energy and substrate replenishment for brain activity, such as glutamate and lipid synthesis. In addition, the glucose metabolism, carried out in the astroglial cytoplasm, result in products such as lactate, methylglyoxal, and glutathione (GSH), which modulate receptors or channels in neurons. Glucose has four potential destinations in neural cells and it is possible, didactically, to conceive a crossroad in “X” to analyze their four destinations. Glucose-6P can be used either for glycogen synthesis or the pentose phosphate pathway, right and left arm of the X, respectively. Fructose-6P is the continuity of glycolysis until pyruvate, as well as the initial compound of the hexosamine pathway, which represent right and left legs of the X, respectively. We evaluated each glucose destination and its regulation, pointing out the products of these pathways and how they can affect synaptic communication. Extracellular L-lactate, either generated from glucose or from glycogen, binds to HCAR1, a specific receptor abundantly localized in perivascular and post-synaptic membranes regulating synaptic plasticity. Methylglyoxal, a product of a deviation of glycolysis, as well as its derivative D-lactate, are also released by astrocytes and bind to GABAA receptors and HCAR1, respectively. GSH, beyond its antioxidant role, also binds to ionotropic glutamate receptors in the synaptic cleft. Finally, we examined the hexosamine pathway and evaluated the effect of GlcNAc-modification on key proteins that regulate the other glucose destinations.

Keywords: astrocyte, Glycolysis, GSH, Lactate, methylglyoxal, neurotransmission

Received: 31 Oct 2018; Accepted: 20 Dec 2018.

Edited by:

Rubem C. Guedes, Federal University of Pernambuco, Brazil

Reviewed by:

Angus M. Brown, University of Nottingham, United Kingdom
Brenda Bartnik-Olson, Loma Linda University, United States  

Copyright: © 2018 Gonçalves, Rodrigues, Bobermin, Zanotto, Vizuete, Quincozes-Santos, Souza and Leite. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: MD, PhD. Carlos-Alberto Gonçalves, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil, casg@ufrgs.br