title: Brain region-specific perfluoroalkylated sulfonate (PFSA) and carboxylic acid (PFCA) accumulation and neurochemical biomarker responses in east Greenland polar bears (Ursus maritimus).
abstract: Perfluoroalkyl substances (PFASs) is a growing class of contaminants in the Arctic environment, and include the established perfluorinated sulfonates (PFSAs; especially perfluorooctane sulfonate (PFOS)) and carboxylic acids (PFCAs). PFSAs and PFCAs of varying chain length have been reported to bioaccumulate in lipid rich tissues of the brain among other tissues such as liver, and can reach high concentrations in top predators including the polar bear. PFCA and PFSA bioaccummulation in the brain has the potential to pose neurotoxic effects and therefore we conducted a study to investigate if variations in neurochemical transmitter systems i.e. the cholinergic, glutaminergic, dopaminergic and GABAergic, could be related to brain-specific bioaccumulation of PFASs in East Greenland polar bears. Nine brain regions from nine polar bears were analyzed for enzyme activity (monoamine oxidase (MAO), acetylcholinesterase (AChE) and glutamine synthetase (GS)) and receptor density (dopamine-2 (D2), muscarinic cholinergic (mAChR) and gamma-butyric acid type A (GABA-A)) along with PFSA and PFCA concentrations. Average brain ∑PFSA concentration was 25ng/g ww where PFOS accounted for 91%. Average ∑PFCA concentration was 88ng/g ww where PFUnDA, PFDoDA and PFTrDA combined accounted for 79%. The highest concentrations of PFASs were measured in brain stem, cerebellum and hippocampus. Correlative analyses were performed both across and within brain regions. Significant positive correlations were found between PFASs and MAO activity in occipital lobe (e.g. ∑PFCA; rp=0.83, p=0.041, n=6) and across brain regions (e.g. ∑PFCA; rp=0.47, p=0.001, ∑PFSA; rp=0.44, p>0.001; n=50). GABA-A receptor density was positively correlated with two PFASs across brain regions (PFOS; rp=0.33, p=0.02 and PFDoDA; rp=0.34, p=0.014; n=52). Significant negative correlations were found between mAChR density and PFASs in cerebellum (e.g. ∑PFCA; rp=-0.95, p=0.013, n=5) and across brain regions (e.g. ∑PFCA; rp=-0.40, p=0.003, ∑PFSA; rp=-0.37, p=0.007; n=52). AChE activity and D2 density were negatively correlated with single PFCAs in several brain regions, whereas GS activity was positively correlated with PFASs primarily in occipital lobe. Results from the present study support the hypothesis that PFAS concentrations in polar bears from East Greenland have exceeded the threshold limits for neurochemical alterations. It is not known whether the observed alterations in neurochemical signaling are currently having negative effects on neurochemistry in East Greenland polar bears. However given the importance of these systems in cognitive processes and motor function, the present results indicate an urgent need for a better understanding of neurochemical effects of PFAS exposure to wildlife.
authors: Toxicology Laboratory, Section of Advanced Drug Analysis, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: hct186@alumni.ku.dk.
authors: Kathrine
authors: K
authors: Eggers Pedersen
authors: Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Quebec, Canada.
authors: Niladri
authors: N
authors: Basu
authors: Wildlife and Landscape Science Directorate, Science and Technology Branch, Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, ON, Canada.
authors: Robert
authors: R
authors: Letcher
authors: Wildlife and Landscape Science Directorate, Science and Technology Branch, Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, ON, Canada.
authors: Alana K
authors: AK
authors: Greaves
authors: Aarhus University, Faculty of Science and Technology, Department of Bioscience, Arctic Research Centre, Roskilde, Denmark.
authors: Christian
authors: C
authors: Sonne
authors: Aarhus University, Faculty of Science and Technology, Department of Bioscience, Arctic Research Centre, Roskilde, Denmark.
authors: Rune
authors: R
authors: Dietz
authors: Toxicology Laboratory, Section of Advanced Drug Analysis, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Bjarne
authors: B
authors: Styrishave
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D017738:Alkanesulfonic Acids / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002264:Carboxylic Acids / Q000032:analysis / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004781:Environmental Exposure; D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D006116:Greenland; D008297:Male; D013058:Mass Spectrometry; D008995:Monoamine Oxidase / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D001503:Ursidae / Q000378:metabolism*
chemical_list: D017738:Alkanesulfonic Acids; D015415:Biomarkers; D002264:Carboxylic Acids; D004785:Environmental Pollutants; D017981:Receptors, Neurotransmitter; D008995:Monoamine Oxidase; D000110:Acetylcholinesterase; D005974:Glutamate-Ammonia Ligase
keywords: Brain; Neurotoxicology; Perfluorinated substances; Polar bear (Ursus maritimus)