Journal article
Dietary Supplementation with Milk Lipids Leads to Suppression of Developmental and Behavioral Phenotypes of Hyperexcitable Drosophila Mutants
Neuroscience, Vol.520, pp.1-17
06/2023
DOI: 10.1016/j.neuroscience.2023.03.027
PMCID: PMC10200772
PMID: 37004908
Abstract
•Feeding Drosophila mutants a small amount of milk lipids can suppress seizures.•Part of the seizure-suppressing effects of milk lipids is due to α-linolenic acid.•Feeding lipids during larval stages effectively suppresses adult seizures.•Feeding lipids rescues neurodevelopmental defects in seizure mutants.
Dietary modifications often have a profound impact on the penetrance and expressivity of neurological phenotypes that are caused by genetic defects. Our previous studies in Drosophila melanogaster revealed that seizure-like phenotypes of gain-of-function voltage-gated sodium (Nav) channel mutants (paraShu, parabss1, and paraGEFS+), as well as other seizure-prone “bang-sensitive” mutants (eas and sda), were drastically suppressed by supplementation of a standard diet with milk whey. In the current study we sought to determine which components of milk whey are responsible for the diet-dependent suppression of their hyperexcitable phenotypes. Our systematic analysis reveals that supplementing the diet with a modest amount of milk lipids (0.26% w/v) mimics the effects of milk whey. We further found that a minor milk lipid component, α-linolenic acid, contributed to the diet-dependent suppression of adult paraShu phenotypes. Given that lipid supplementation during the larval stages effectively suppressed adult paraShu phenotypes, dietary lipids likely modify neural development to compensate for the defects caused by the mutations. Consistent with this notion, lipid feeding fully rescued abnormal dendrite development of class IV sensory neurons in paraShu larvae. Overall, our findings demonstrate that milk lipids are sufficient to ameliorate hyperexcitable phenotypes in Drosophila mutants, providing a foundation for future investigation of the molecular and cellular mechanisms by which dietary lipids modify genetically induced abnormalities in neural development, physiology, and behavior.
Details
- Title: Subtitle
- Dietary Supplementation with Milk Lipids Leads to Suppression of Developmental and Behavioral Phenotypes of Hyperexcitable Drosophila Mutants
- Creators
- Junko Kasuya - Department of Anesthesia, United StatesWayne Johnson - Department of Molecular Physiology and Biophysics, Carver College of Medicine, United StatesHung-Lin Chen - Interdisciplinary Graduate Program in Genetics, University of Iowa, IA 52242, United StatesToshihiro Kitamoto - Department of Anesthesia, United States
- Resource Type
- Journal article
- Publication Details
- Neuroscience, Vol.520, pp.1-17
- DOI
- 10.1016/j.neuroscience.2023.03.027
- PMID
- 37004908
- PMCID
- PMC10200772
- NLM abbreviation
- Neuroscience
- ISSN
- 0306-4522
- eISSN
- 1873-7544
- Publisher
- Elsevier Ltd
- Language
- English
- Electronic publication date
- 03/31/2023
- Date published
- 06/2023
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Anesthesia; Neuroscience and Pharmacology
- Record Identifier
- 9984386254002771
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