Journal article
Commensal bacteria exacerbate seizure‐like phenotypes in Drosophila voltage‐gated sodium channel mutants
Genes, brain and behavior, Vol.23(5), e70000
09/04/2024
DOI: 10.1111/gbb.70000
PMCID: PMC11373613
PMID: 39231190
Appears in UI Libraries Support Open Access
Abstract
Mutations in voltage-gated sodium (Nav) channels, which are essential for generating and propagating action potentials, can lead to serious neurological disorders, such as epilepsy. However, disease-causing Nav channel mutations do not always result in severe symptoms, suggesting that the disease conditions are significantly affected by other genetic factors and various environmental exposures, collectively known as the “exposome”. Notably, recent research emphasizes the pivotal role of commensal bacteria in neural development and function. Although these bacteria typically benefit the nervous system under normal conditions, their impact during pathological states remains largely unknown. Here, we investigated the influence of commensal microbes on seizure-like phenotypes exhibited by paraShu—a gain-of-function mutant of the Drosophila Nav channel gene, paralytic. Remarkably, the elimination of endogenous bacteria considerably ameliorated neurological impairments in paraShu. Consistently, reintroducing bacteria, specifically from the Lactobacillus or Acetobacter genera, heightened the phenotypic severity in the bacteria-deprived mutants. These findings posit that particular native bacteria contribute to the severity of seizure-like phenotypes in paraShu. We further uncovered that treating paraShu with antibiotics boosted Nrf2 signaling in the gut, and that global Nrf2 activation mirrored the effects of removing bacteria from paraShu. This raises the possibility that the removal of commensal bacteria suppresses the seizure-like manifestations through augmented antioxidant responses. Since bacterial removal during development was critical for suppression of adult paraShu phenotypes, our research sets the stage for subsequent studies, aiming to elucidate the interplay between commensal bacteria and the developing nervous system in conditions predisposed to the hyperexcitable nervous system.
Details
- Title: Subtitle
- Commensal bacteria exacerbate seizure‐like phenotypes in Drosophila voltage‐gated sodium channel mutants
- Creators
- Patrick Lansdon - University of IowaJunko Kasuya - University of IowaToshihiro Kitamoto - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Genes, brain and behavior, Vol.23(5), e70000
- Publisher
- Wiley
- DOI
- 10.1111/gbb.70000
- PMID
- 39231190
- PMCID
- PMC11373613
- ISSN
- 1601-1848
- eISSN
- 1601-183X
- Grant note
- National Institutes of Health: R21 NS101542, R03 NS101541, R21 NS127364, T32 NS045549
National Institutes of Health, Grant/Award Numbers: R21 NS101542, R03 NS101541, R21 NS127364, T32 NS045549
- Language
- English
- Date published
- 09/04/2024
- Academic Unit
- Iowa Neuroscience Institute; Anesthesia; Neuroscience and Pharmacology
- Record Identifier
- 9984701859902771
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