Gut microbiota modulates expression of genes involved in the astrocyte-neuron lactate shuttle in the hippocampus
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Supplementary Materials
Date
2020-12
Authors
Margineanu, Michael B.
Sherwin, Eoin
Golubeva, Anna V.
Peterson, Veronica L.
Hoban, Alan E.
Fiumelli, Hubert
Rea, Kieran
Cryan, John F.
Magistretti, Pierre J.
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Volume Title
Publisher
Elsevier B.V.
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Abstract
The gut microbiota modulates brain physiology, development, and behavior and has been implicated as a key regulator in several central nervous system disorders. Its effect on the metabolic coupling between neurons and astrocytes has not been studied to date, even though this is an important component of brain energy metabolism and physiology and it is perturbed in neurodegenerative and cognitive disorders. In this study, we have investigated the mRNA expression of 6 genes encoding proteins implicated in the astrocyte-neuron lactate shuttle (Atp1a2, Ldha, Ldhb, Mct1, Gys1, Pfkfb3), in relation to different gut microbiota manipulations, in the mouse brain hippocampus, a region with critical functions in cognition and behavior. We have discovered that Atp1a2 and Pfkfb3, encoding the ATPase, Na+/K+ transporting, alpha 2 subunit, respectively and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3, two genes predominantly expressed in astrocytes, were upregulated in the hippocampus after microbial colonization of germ-free mice for 24 h, compared with conventionally raised mice. Pfkfb3 was also upregulated in germ-free mice compared with conventionally raised mice, while an increase in Atp1a2 expression in germ-free mice was confirmed only at the protein level by Western blot. In a separate cohort of mice, Atp1a2 and Pfkfb3 mRNA expression was upregulated in the hippocampus following 6-week dietary supplementation with prebiotics (fructoand galactooligosaccharides) in an animal model of chronic psychosocial stress. To our knowledge, these findings are the first to report an influence of the gut microbiota and prebiotics on mRNA expression of genes implicated in the metabolic coupling between neurons and astrocytes. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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Keywords
Aerobic glycolysis , Brain , Metabolism , Absence , Gut microbiota , Brain energy metabolism , Hippocampus , Astrocyte-neuron lactate shuttle
Citation
Margineanu, M. B., Sherwin, E., Golubeva, A. V., Peterson, V. L., Hoban, A. E., Fiumelli, H., Rea, K., Cryan, J. F. and Magistretti, P. J. (2020) 'Gut microbiota modulates expression of genes involved in the astrocyte-neuron lactate shuttle in the hippocampus', European Neuropsychopharmacology, 41, pp. 152-159. doi: 10.1016/j.euroneuro.2020.11.006