Gut metabolite S-equol ameliorates hyperexcitability in entorhinal cortex neurons following Theiler murine encephalomyelitis virus-induced acute seizures

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dc.contributor.authorGallucci, Allisonen
dc.contributor.authorPatel, Dipan C.en
dc.contributor.authorThai, K'Ehleyren
dc.contributor.authorTrinh, Jonathanen
dc.contributor.authorGude, Rosalieen
dc.contributor.authorShukla, Devikaen
dc.contributor.authorCampbell, Susan L.en
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.contributor.departmentSchool of Neuroscienceen
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.date.accessioned2021-07-21T14:28:40Zen
dc.date.available2021-07-21T14:28:40Zen
dc.date.issued2021-07-02en
dc.description.abstractObjective A growing body of evidence indicates a potential role for the gut-brain axis as a novel therapeutic target in treating seizures. The present study sought to characterize the gut microbiome in Theiler murine encephalomyelitis virus (TMEV)-induced seizures, and to evaluate the effect of microbial metabolite S-equol on neuronal physiology as well as TMEV-induced neuronal hyperexcitability ex vivo. Methods We infected C57BL/6J mice with TMEV and monitored the development of acute behavioral seizures 0-7 days postinfection (dpi). Fecal samples were collected at 5-7 dpi and processed for 16S sequencing, and bioinformatics were performed with QIIME2. Finally, we conducted whole-cell patch-clamp recordings in cortical neurons to investigate the effect of exogenous S-equol on cell intrinsic properties and neuronal hyperexcitability. Results We demonstrated that gut microbiota diversity is significantly altered in TMEV-infected mice at 5-7 dpi, exhibiting separation in beta diversity in TMEV-infected mice dependent on seizure phenotype, and lower abundance of genus Allobaculum in TMEV-infected mice regardless of seizure phenotype. In contrast, we identified specific loss of S-equol-producing genus Adlercreutzia as a microbial hallmark of seizure phenotype following TMEV infection. Electrophysiological recordings indicated that exogenous S-equol alters cortical neuronal physiology. We found that entorhinal cortex neurons are hyperexcitable in TMEV-infected mice, and exogenous application of microbial-derived S-equol ameliorated this TMEV-induced hyperexcitability. Significance Our study presents the first evidence of microbial-derived metabolite S-equol as a potential mechanism for alteration of TMEV-induced neuronal excitability. These findings provide new insight for the novel role of S-equol and the gut-brain axis in epilepsy treatment.en
dc.description.notesCollege of Agricultural and Life Sciences at Virginia Tech; School of Neuroscience at Virginia Tech; Virginia Tech Insitute for Critical Technology and Applied Science (ICTAS)en
dc.description.sponsorshipCollege of Agricultural and Life Sciences at Virginia Tech; School of Neuroscience at Virginia Tech; Virginia Tech Insitute for Critical Technology and Applied Science (ICTAS)en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1111/epi.16979en
dc.identifier.eissn1528-1167en
dc.identifier.issn0013-9580en
dc.identifier.pmid34212377en
dc.identifier.urihttp://hdl.handle.net/10919/104241en
dc.language.isoenen
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectelectrophysiologyen
dc.subjectgut-brain axisen
dc.subjectseizuresen
dc.subjectS-equolen
dc.subjectTMEVen
dc.titleGut metabolite S-equol ameliorates hyperexcitability in entorhinal cortex neurons following Theiler murine encephalomyelitis virus-induced acute seizuresen
dc.title.serialEpilepsiaen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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