Gut microbiota modulates expression of genes involved in the astrocyte-neuron lactate shuttle in the hippocampus.
Type
ArticleAuthors
Margineanu, Michael B.
Sherwin, Eoin
Golubeva, Anna
Peterson, Veronica
Hoban, Alan
Fiumelli, Hubert

Rea, Kieran
Cryan, John F
Magistretti, Pierre J.

KAUST Department
Bioscience ProgramBiological and Environmental Sciences and Engineering (BESE) Division
Date
2020-11-13Online Publication Date
2020-11-13Print Publication Date
2020-11Submitted Date
2019-10-17Permanent link to this record
http://hdl.handle.net/10754/666014
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Show full item recordAbstract
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 sub-unit, 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 (fructo- and galacto-oligosaccharides) 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.Citation
Margineanu, M. B., Sherwin, E., Golubeva, A., Peterson, V., Hoban, A., Fiumelli, H., … Magistretti, P. J. (2020). Gut microbiota modulates expression of genes involved in the astrocyte-neuron lactate shuttle in the hippocampus. European Neuropsychopharmacology. doi:10.1016/j.euroneuro.2020.11.006Publisher
Elsevier BVJournal
European neuropsychopharmacology : the journal of the European College of NeuropsychopharmacologyPubMed ID
33191074Additional Links
https://linkinghub.elsevier.com/retrieve/pii/S0924977X20309408ae974a485f413a2113503eed53cd6c53
10.1016/j.euroneuro.2020.11.006
Scopus Count
Except where otherwise noted, this item's license is described as This is an open access article under the CC BY-NC-ND license.
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