Alteration of neuro-dopamine and steroid hormone homeostasis in wild Bank voles in relation to tissue concentrations of PFAS at a Nordic skiing area

Neurotransmission Targets of Per- and Polyfluoroalkyl Substance Neurotoxicity: Mechanisms and Potential Implications for Adverse Neurological Outcomes

“…There is growing evidence that PFOS, PFOA, and PFAS mixtures lead to changes in neurotransmitter levels, ,− alter neurotransmitter receptor and transporter expression and function, ,,,,,− and change neurotransmitter metabolism. ,− ,,,,,,,,,, Although the major focus for the evaluation of PFAS neurotoxicity has been on PFAS developmental neurotoxicity, ,,,− ,− ,,,,,,,,− PFAS exposure during both development and adulthood may change neurotransmitter levels in a brain region-specific manner (Table ). Lifelong exposure of humans to PFAS may result in dynamic changes in neurological function resulting from PFAS accumulation over time.…”

“…In the studies utilizing sentinel species exposed to PFAS in feed during late or early brain development (Atlantic cod and northern leopard frogs) as well as mice fed a PFAS mix starting at weaning, the whole brain dopamine levels decreased. − An exception was a vole study that found PFAS levels to be positively associated with dopamine levels (negatively associated with the metabolite/parent neurotransmitter ratio). Importantly, this was a sentinel study with uncontrolled exposures, where a ski area with voles containing elevated PFOS, PFHxS, PFDA, PFUA, perfluorododecanoic acid (PFDoDA), perfluorotridecanoic acid (PFTrDA), and perfluorotetradecanoic acid (PFTeDA) was compared to a reference area with voles that had elevated PFHxA; , thus, the study compared two different PFAS mixes without a control. With respect to the sentinel vole study, the same group conducted a controlled exposure in mice on the basis of PFAS earthworm levels in a contaminated ski area and found the PFAS exposure to be associated with decreased whole brain dopamine levels similar to other sentinel studies. − ,, Another laboratory study that dosed male mice with PFOA during adolescence found elevation in whole brain dopamine .…”

“…Importantly, this was a sentinel study with uncontrolled exposures, where a ski area with voles containing elevated PFOS, PFHxS, PFDA, PFUA, perfluorododecanoic acid (PFDoDA), perfluorotridecanoic acid (PFTrDA), and perfluorotetradecanoic acid (PFTeDA) was compared to a reference area with voles that had elevated PFHxA; , thus, the study compared two different PFAS mixes without a control. With respect to the sentinel vole study, the same group conducted a controlled exposure in mice on the basis of PFAS earthworm levels in a contaminated ski area and found the PFAS exposure to be associated with decreased whole brain dopamine levels similar to other sentinel studies. − ,, Another laboratory study that dosed male mice with PFOA during adolescence found elevation in whole brain dopamine . Taken together, these studies suggest the effects of PFAS on dopamine levels during development may depend on the exposure of one or more PFAS.…”

“…Recent studies have been evaluating metabolism-related mechanisms to explain PFAS-induced changes in neurotransmitter levels. The monoamine neurotransmitters include norepinephrine, dopamine, and serotonin and share metabolic enzymes and precursors. , There is evidence in the animal data that PFAS exposure changes monoamine metabolism. ,− ,,,,,,, Multiple studies demonstrated PFOS-treated male rats had decreased dopamine or serotonin turnover in the hypothalamus , and hippocampus . Studies that developmentally exposed northern leopard frog tadpoles to PFOS or PFOA found no changes in whole-brain serotonin levels or serotonin turnover. , This suggests that the effects of PFAS on monoamine metabolism may depend on the species and brain region.…”

“…Ongoing research has identified that the PFAS’s neurotoxic targets for neurotransmission alter neurotransmitter levels, ,− synaptic protein expression and function, ,,,,,− and calcium signaling. − ,,− This Review aims to critically analyze the state of PFAS neurotoxicity with focus on neurotransmission-related end points and to reveal PFAS’s potential targets of neurological disease that require epidemiological evaluation in the future. Recent reviews have broadly focused on brain accumulation and neurotoxicity. ,,− This critical analysis of the field focuses specifically on neurotransmission targets, which may underlie adverse neurological outcomes.…”