Exposure to bisphenol A differentially impacts neurodevelopment and behavior in Drosophila melanogaster from distinct genetic backgrounds

[Display omitted] •Exposure to bisphenol A (BPA) in Drosophila melanogaster impacted behavior, axon guidance, and neuroblast development.•BPA-exposure caused mutant phenotypes in w1118 flies.•BPA either had no significant impact or exhibited rescue effects in the Fragile X syndrome (FXS) Drosophila...

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Published in:	Neurotoxicology (Park Forest South) Vol. 82; pp. 146 - 157
Main Authors:	Nguyen, U., Tinsley, B., Sen, Y., Stein, J., Palacios, Y., Ceballos, A., Welch, C., Nzenkue, K., Penn, A., Murphy, L., Leodones, K., Casiquin, J., Ivory, I., Ghenta, K., Danziger, K., Widman, E., Newman, J., Triplehorn, M., Hindi, Z., Mulligan, K.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 01-01-2021
Subjects:	Axon guidance Behavior Bisphenol A Drosophila melanogaster Fragile X syndrome Neuroblasts Bisphenol A Fragile X syndrome Behavior Axon guidance Neuroblasts Drosophila melanogaster
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Summary:	[Display omitted] •Exposure to bisphenol A (BPA) in Drosophila melanogaster impacted behavior, axon guidance, and neuroblast development.•BPA-exposure caused mutant phenotypes in w1118 flies.•BPA either had no significant impact or exhibited rescue effects in the Fragile X syndrome (FXS) Drosophila model.•BPA exposure increased embryonic-to-pupal lethality in w1118 flies, but had no impact on early lethality of FXS flies. Bisphenol A (BPA) is a ubiquitous environmental chemical that has been linked to behavioral differences in children and shown to impact critical neurodevelopmental processes in animal models. Though data is emerging, we still have an incomplete picture of how BPA disrupts neurodevelopment; in particular, how its impacts may vary across different genetic backgrounds. Given the genetic tractability of Drosophila melanogaster, they present a valuable model to address this question. Fruit flies are increasingly being used for assessment of neurotoxicants because of their relatively simple brain structure and variety of measurable behaviors. Here we investigated the neurodevelopmental impacts of BPA across two genetic strains of Drosophila—w1118 (control) and the Fragile X Syndrome (FXS) model—by examining both behavioral and neuronal phenotypes. We show that BPA induces hyperactivity in larvae, increases repetitive grooming behavior in adults, reduces courtship behavior, impairs axon guidance in the mushroom body, and disrupts neural stem cell development in the w1118 genetic strain. Remarkably, for every behavioral and neuronal phenotype examined, the impact of BPA in FXS flies was either insignificant or contrasted with the phenotypes observed in the w1118 strain. This data indicates that the neurodevelopmental impacts of BPA can vary widely depending on genetic background and suggests BPA may elicit a gene-environment interaction with Drosophila fragile X mental retardation 1 (dFmr1)—the ortholog of human FMR1, which causes Fragile X Syndrome and is associated with autism spectrum disorder.
Bibliography:	Currently at the Department of Cell and Molecular Biology, University of California, Berkeley
ISSN:	0161-813X 1872-9711
DOI:	10.1016/j.neuro.2020.12.007