Brain region-specific perfluoroalkylated sulfonate (PFSA) and carboxylic acid (PFCA) accumulation and neurochemical biomarker Responses in east Greenland polar Bears (Ursus maritimus)

Kathrine Eggers Pedersen; Niladri Basu; Robert Letcher; Alana K. Greaves; Christian Sonne; Rune Dietz; Bjarne Styrishave

doi:10.1016/j.envres.2015.01.015

Brain region-specific perfluoroalkylated sulfonate (PFSA) and carboxylic acid (PFCA) accumulation and neurochemical biomarker Responses in east Greenland polar Bears (Ursus maritimus)

Kathrine Eggers Pedersen, Niladri Basu, Robert Letcher, Alana K. Greaves, Christian Sonne, Rune Dietz, Bjarne Styrishave

Section for Organismal Biology

38 Citations (Scopus)

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.

Original language	English
Journal	Environmental Research
Volume	138
Pages (from-to)	22-31
Number of pages	10
ISSN	0013-9351
DOIs	https://doi.org/10.1016/j.envres.2015.01.015
Publication status	Published - 1 Apr 2015

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Brain region-specific perfluoroalkylated sulfonate (PFSA) and carboxylic acid (PFCA) accumulation and neurochemical biomarker Responses in east Greenland polar Bears (Ursus maritimus). / Pedersen, Kathrine Eggers; Basu, Niladri; Letcher, Robert et al.

In: Environmental Research, Vol. 138, 01.04.2015, p. 22-31.

Research output: Contribution to journal › Journal article › Research › peer-review

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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.",

author = "Pedersen, {Kathrine Eggers} and Niladri Basu and Robert Letcher and Greaves, {Alana K.} and Christian Sonne and Rune Dietz and Bjarne Styrishave",

year = "2015",

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day = "1",

doi = "10.1016/j.envres.2015.01.015",

language = "English",

volume = "138",

pages = "22--31",

journal = "Environmental Research",

issn = "0013-9351",

publisher = "Academic Press",

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T1 - Brain region-specific perfluoroalkylated sulfonate (PFSA) and carboxylic acid (PFCA) accumulation and neurochemical biomarker Responses in east Greenland polar Bears (Ursus maritimus)

AU - Pedersen, Kathrine Eggers

AU - Basu, Niladri

AU - Letcher, Robert

AU - Greaves, Alana K.

AU - Sonne, Christian

AU - Dietz, Rune

AU - Styrishave, Bjarne

PY - 2015/4/1

Y1 - 2015/4/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.envres.2015.01.015

DO - 10.1016/j.envres.2015.01.015

M3 - Journal article

C2 - 25682255

SN - 0013-9351

VL - 138

SP - 22

EP - 31

JO - Environmental Research

JF - Environmental Research

ER -

Brain region-specific perfluoroalkylated sulfonate (PFSA) and carboxylic acid (PFCA) accumulation and neurochemical biomarker Responses in east Greenland polar Bears (Ursus maritimus)

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