Abstract

Per- and polyfluoralkyl substances (PFAS) are a diverse class of anthropogenic “forever chemicals” of major public health concern due to their widespread use, long environmental and biological half-lives, presence in human plasma, and multiple links to adverse health outcomes.¹ They have been found in the brains of wildlife and the literature supports their potential neurotoxicity. The northern leopard frog (Rana pipiens) has been specifically selected to evaluate the hypothesized exacerbated effects of PFAS on neurodegenerative diseases. Unlike the traditional toxicological models (e.g., nematodes, fly, mouse, and rat), R. pipiens produce human-like neuromelanin (NM), a pigment in the brain’s substantia nigra that modulates neurodegenerative diseases, such as Parkinson’s disease.² PFAS has been proven to cross the blood-brain barrier and accumulate in the brain of this species.³ Developmental exposure to PFAS, specifically perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), was also shown to selectively decrease brain dopamine levels and produce complex changes within neurotransmitter systems in R. pipiens.⁴ A reference R. pipiens genome was assembled to track neurotoxic mechanisms and sublethal responses following PFAS exposure. This assembly will permit the analysis of gene expression changes in the brain following PFAS exposure and whether these genes and their pathways may be novel or linked to neurodegenerative disease candidates proposed in traditional toxicological models and humans.

Acknowledgments

The authors wish to thank the Strategic Environmental Research and Development Program, Department of Defense, United States of America, and the Ralph W. and Grace M. Showalter Research Trust, United States of America, for their contributions to this comprehensive study.

*Presenting author
+Student presenter

Literature Cited

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3.  Foguth RM, Hoskins TD, Clark GC, Nelson M, Flynn RW, de Perre C, Hoverman JT, Lee LS, Sepúlveda MS, Cannon JR. Single and mixture per- and polyfluoroalkyl substances accumulate in developing northern leopard frog brains and produce complex neurotransmission alterations. Neurotoxicol Teratol. 2020;81:106907.

4.  Foguth RM, et al. Developmental exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) selectively decreases brain dopamine levels in northern leopard frogs. Toxicol Appl Pharmacol. 2019;377:114623.