Per- and polyfluoroalkyl substances (PFAS) are present in water and >99% of human serum. They are found in brains of wildlife; however, little is known about effects on the developing brain. To determine the effects of PFAS on brain and cardiac innervation, we conducted an outdoor mesocosm experiment with Northern leopard frog larvae (Rana pipiens) exposed to control, 10ppb perfluorooctane sulfonate (PFOS), or a PFAS mixture totaling 10ppb that mimicked aqueous film forming foam-impacted surface water (4ppb PFOS, 3ppb perfluorohexane sulfonate, 1.25ppb perfluorooctanoate, 1.25ppb perfluorohexanoate, and 0.5ppb perfluoro-n-pentanoate). Water was spiked with PFAS and 25 larvae (Gosner stage (GS) 25) added to each mesocosm (n=4 mesocosms per treatment). After 30days, we harvested eight brains per mesocosm and remaining larvae developed to GS 46 (i.e. metamorphosis) before brains and hearts were collected. Weight, length, GS, and time to metamorphosis were recorded. Brain concentrations of all five PFAS were quantified using LC/MS/MS. Dopamine and metabolites, serotonin and its metabolite, norepinephrine, gamma-aminobutyric acid, and glutamate were quantified using High Performance Liquid Chromatography with electrochemical detection while acetylcholine and acetylcholinesterase activity were quantified with the Invitrogen Amplex Red Acetylcholine Assay. PFOS accumulated in the brain time- and dose-dependently. After 30days, the mixture decreased serotonin while both PFAS treatments decreased glutamate. Interestingly, acetylcholine increased in PFAS treatments at GS 46. This research shows that developmental environmentally relevant exposure to PFAS changes neurotransmitters, especially acetylcholine.
        
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Foguth RM, Hoskins TD, Clark GC, Nelson M, Flynn RW, de Perre C, Hoverman JT, Lee LS, Sepulveda MS, Cannon JR (2020) Single and mixture per- and polyfluoroalkyl substances accumulate in developing Northern leopard frog brains and produce complex neurotransmission alterations Neurotoxicology & Teratology
Foguth RM, Hoskins TD, Clark GC, Nelson M, Flynn RW, de Perre C, Hoverman JT, Lee LS, Sepulveda MS, Cannon JR (2020) Neurotoxicology & Teratology