Neurobehavioral teratogenicity of perfluorinated alkyls in an avian model

Abstract

Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Pinkas, A., Slotkin, T. A., Brick-Turin, Y., Van der Zee, E. A., & Yanai, J. (2010). Neurobehavioral teratogenicity of perfluorinated alkyls in an avian model. Neurotoxicology and Teratology, 32(2), 182-186. https://doi.org/10.1016/j.ntt.2009.11.004 Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Perfluorinated alkyls are widely-used agents that accumulate in ecosystems and organisms because of their slow rate of degradation. There is increasing concern that these agents may be developmental neurotoxicants and the present study was designed to develop an avian model for the neurobehavioral teratogenicity of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Fertilized chicken eggs were injected with 5 or 10 mg/kg of either compound on incubation day 0. On the day of hatching, imprinting behavior was impaired by both compounds. We then explored underlying mechanisms involving the targeting of protein kinase C (PKC) isoforms (α, β, γ) in the intermedial part of the hyperstriatum ventrale, the region most closely associated with imprinting. With PFOA exposure, cytosolic PKC concentrations were significantly elevated for all three isoforms; despite the overall increase in PKC expression, membrane-associated PKC was unaffected, indicating a defect in PKC translocation. In contrast, PFOS exposure evoked a significant decrease in cytosolic PKC, primarily for the β and γ isoforms, but again without a corresponding change in membrane-associated enzyme; this likely partial, compensatory increases in translocation to offset the net PKC deficiency. Our studies indicate that perfluorinated alkyls are indeed developmental neurotoxicants that affect posthatch cognitive performance but that the underlying synaptic mechanisms may differ substantially among the various members of this class of compounds, setting the stage for disparate outcomes later in life.

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

“…Effects were most pronounced for individuals exposed during development (Johansson et al, 2009(Johansson et al, , 2008. At the molecular level, correlations have been found between exposure to PFOS or PFOA and changes in the cholinergic system in rodents (Johansson et al, 2008) and protein kinase C (involved in neurotransmission by G protein-coupled receptors) in hatchlings (Pinkas et al, 2010). Taken together, these findings suggest that PFASs may disrupt the function of the nervous system.…”

Toxicological Effects of Perfluoroalkyl and Polyfluoroalkyl Substances

“…The PFOS induced apoptosis was connected to activation of different subtypes of protein kinase C (PKC-α, PKC-βII and PKC-ε). The effect of PFOS and PFOA on PKC-translocation was also observed by Pinkas et al ( 2010 ) on developmentally exposed chicks as described in the previous section. PKC is involved in a range of processes in the brain such as cognitive functions, learning and memory and several of studies have shown that other environmental toxicants, such as PCBs, dioxins and brominated fl ame retardants also infl uence PKC activity (Kodavanti et al 1994 ).…”

“…Different PKC isoforms have previously been postulated as possible targets following both adult and developmental exposure to halogenated aromatic hydrocarbons, such as the PCBs (Kodavanti et al 1994(Kodavanti et al , 1998Yang et al 2003 ). The doses used in the experiment by Pinkas et al ( 2010 ) lead, however to high mortality. Between 30 and 50 % of the exposed eggs did not develop embryos indicating that the doses used were detrimental to the chicks leading to other substantial non-neurotoxic effects.…”

“…Pinkas and co-workers exposed chicks prenatally to single doses of PFOS and PFOA at incubation day 0 for 5 and 10 mg/kg (Pinkas et al 2010 ). The chicks were subjected to behavioral testing at hatching day 1 and showed impaired imprinting behavior.…”

Per- and polyfluorinated substances in the Nordic Countries

“…Neonatal exposure of mice to PFOA (and PFOS) affected the proteins involved in neurogenesis and synaptogenesis in the developing mouse brain, which were accompanied by neurobehavioral defects in adulthood (Johansson et al, 2008). Also in an avian model PFOA was reported to be a developmental neurotoxicant (Pinkas et al, 2010). In summary, PFOA exposures in rodent indicate carcinogenic responses in liver, pancreas, testes and mammary glands.…”