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dc.contributor.authorMargineanu, Michael B.
dc.contributor.authorSherwin, Eoin
dc.contributor.authorGolubeva, Anna
dc.contributor.authorPeterson, Veronica
dc.contributor.authorHoban, Alan
dc.contributor.authorFiumelli, Hubert
dc.contributor.authorRea, Kieran
dc.contributor.authorCryan, John F
dc.contributor.authorMagistretti, Pierre J.
dc.identifier.citationMargineanu, 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.2020.11.006
dc.description.abstractThe 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.
dc.publisherElsevier BV
dc.rightsThis is an open access article under the CC BY-NC-ND license.
dc.titleGut microbiota modulates expression of genes involved in the astrocyte-neuron lactate shuttle in the hippocampus.
dc.contributor.departmentBioscience Program
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.identifier.journalEuropean Neuropsychopharmacology
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionOncoGen Research Centre, “Pius Brinzeu” County Emergency Hospital, Timisoara, Romania
dc.contributor.institutionDepartment of Functional Sciences, “Victor Babeș” University of Medicine and Pharmacy, Timisoara, Romania.
dc.contributor.institutionAPC Microbiome Ireland, University College Cork, Cork, Ireland.
dc.contributor.institutionDepartment of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
dc.contributor.institutionTeagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland.
kaust.personMargineanu, Michael B.
kaust.personFiumelli, Hubert
kaust.personMagistretti, Pierre J.

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