Zebrafish as a Model for Studying the Developmental Neurotoxicity of Persistent and Emerging Environmental Contaminants

Martin, Nathan Ryan-Cyr

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Year:: 2022
Contributor:: Martin, Nathan Ryan-Cyr (creator); Webb, Ashley (Reader); Pennell, Kurt (Reader); Bartnikas, Thomas (Reader); Creton, Robbert (Reader); Plavicki, Jessica (Advisor); Hahn, Mark (Reader); Brown University. Biology and Medicine: Pathobiology (sponsor)
Genre:: theses
Subject:: Zebrafish; neurodevelopment; Zebrafish Behavior; Environmental toxicology; Perfluorinated chemicals; Neuroscience; brain activity; functional neuroimaging; TCDD
Extent:: xix, 203 p.

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Abstract:: As the release of novel chemicals into the environment outpaces the ability to perform exhaustive toxicological assessments, there is growing concern about the effects of chemical exposure on human health. Increased incidences of neurodevelopmental disorders such as attention-deficit hyperactivity disorder and autism spectrum disorder have underlined the developing brain as a susceptible target of environmental contaminant exposure. Legacy and emerging contaminants of concern must be extensively studied to understand their impacts on neurodevelopment and brain health. This dissertation focuses on the effects of 2, 3, 7, 8 tetrachlorobenzo-[p]-dioxin (TCDD, dioxin) and per- and polyfluoroalkyl substances (PFAS) on embryonic brain development and function. We use the zebrafish as a model to identify novel neurodevelopmental phenotypes resulting from embryonic chemical exposures through an assembly of tools examining morphological, functional, and behavioral endpoints. In Chapter 2, we determined that embryonic TCDD exposure disrupts neural development by decreasing brain size and impairing the formation of neural networks as well as the production of synaptic vesicles. Additionally, we identified essential roles of ahr2 in neural network formation. In Chapter 3, we examined the effects of perfluorooctane sulfonic acid (PFOS) exposure on the development and function of microglia, the innate immune cell of the brain as well as the impacts of PFOS on brain function and anxiety-like behaviors. In Chapter 4, we expanded our purview of PFAS chemicals and determined that long-chain sulfonic acid PFAS pose a risk to early brain function and behavioral output. These studies revealed unknown consequences of developmental contaminant exposures and illustrated the value of the zebrafish model to assess developmental neurotoxicology.
Notes:: Thesis (Ph. D.)--Brown University, 2022

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Citation

Martin, Nathan Ryan-Cyr, "Zebrafish as a Model for Studying the Developmental Neurotoxicity of Persistent and Emerging Environmental Contaminants" (2022). Pathobiology Theses and Dissertations. Brown Digital Repository. Brown University Library. https://repository.library.brown.edu/studio/item/bdr:t4dzsg9c/

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Pathobiology Theses and Dissertations

Theses and Dissertations for the Pathobiology department.
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