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Allison Gallucci's Dissertation Defense (4/27/2021): The gut-brain axis in seizure susceptibility: A role for microbial metabolite S-equol

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Allison Gallucci

Dissertation Defense:  The gut-brain axis in seizure susceptibility: A role for microbial metabolite S-equol

Allison Gallucci

Graduate Student, Virginia Tech Translational Biology, Medicine, and Health
Graduate Research Assistant, Sontheimer Lab, Fralin Biomedical Research Institute at VTC
April 27, 2021 at 2:00 p.m.

About this Dissertation

Epilepsy is a complex, chronic neurological disorder with diverse underlying etiologies characterized by the spontaneous occurrence of seizures. In adults, the leading cause of epilepsy worldwide in central nervous system (CNS) infection, while in neonates the most common cause of seizures is hypoxic/ischemic encephalopathy (HIE). However, in both adults and neonates, current antiepileptic drugs (AEDs) are ineffective in 30-50% of patients, despite the availability of over 20 FDA approved AEDs with diverse molecular targets. This disparity highlights a critical need for novel therapeutics in seizure-susceptibility and epilepsy. The microbes that inhabit gut mucosal surfaces, termed the gut microbiota, have been increasingly implicated in the pathology of neurological diseases including epilepsy. In this dissertation, Gallucci evaluates gut microbiome alterations in the Theiler’s murine encephalomyelitis virus (TMEV) adult mouse model of CNS infection-induced seizures and find decreases in S-equol-producing bacteria in the gut microbiomes of TMEV-infected mice with seizure phenotypes. Gallucci, working with the Sontheimer Lab, additionally characterizes entorhinal cortex (ECTX) pyramidal neuronal hyperexcitability, and demonstrate the ability of exogenous S-equol to ameliorate CNS-infection-induced ECTX neuronal hyperexcitability ex vivo. Finally, Gallucci demonstrates that perinatal and postnatal exposure to antibiotics alters the gut microbiome and increases seizure-susceptibility following HIE exposure in p9/p10 mice, potentially via sex-specific alterations in neuronal function. Together, this dissertation evaluates the gut-brain axis in pediatric and adult mouse models of seizure-susceptibility and identifies the gut metabolite S-equol as a potential target for the treatment of seizures.

More About the Candidate and Project

Education

Virginia Tech Translational Biology, Medicine, and Health, Ph.D. Candidate

University of Alabama, B.S., Psychology

 

Training

Graduate Research Assistant, Sontheimer Lab, Fralin Biomedical Research Institute at VTC

 

Mentors

Harold Sontheimer, Ph.D., Adjunct Professor, Fralin Biomedical Research Institute at VTC
Susan Campell, Ph.D., Assistant Professor, Department of Animal and Poultry Sciences, College of Agriculture and Life Sciences, Virginia Tech

Committee Members

  • Xin Luo, Ph.D., Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine
  • Michelle Olsen, Ph.D., Associate Professor and Director of Graduate Studies, School of Neuroscience, College of Science, Virginia Tech
  • Mark Witcher, M.D., Ph.D., Faculty, Department of Surgery, Virginia Tech Carilion School of Medicine