Possible mechanism of perfluorooctane sulfonate and perfluorooctanoate on the release of calcium ion from calcium stores in primary cultures of rat hippocampal neurons

Liu, Xiaohui; Jin, Yinlong; Liu, Wei; Wang, Faqi; Hao, Shuang

doi:10.1016/j.tiv.2011.04.016

Cited by 69 publications

(55 citation statements)

References 52 publications

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“…PFOSinduced Ca 2+ influx via L-VDCCs has also been observed in studies in primary hippocampal neurons from rat (Liao et al, 2008). In addition to influx of Ca 2+ from the extracellular environment, release of Ca 2+ from intracellular stores has been reported after PFOS exposure in rat hippocampal neurons by Liu et al (2011) where the liberation was mainly occurring through inositol 1,4,5-triphoshate receptors (IP 3 Rs) and ryanodine receptors (RyRs). As Ca 2+ acts as a second messenger it may potentially activate several downstream signaling pathways and events.…”

Section: Discussionmentioning

confidence: 70%

PFOS-induced excitotoxicity is dependent on Ca2+ influx via NMDA receptors in rat cerebellar granule neurons

Berntsen

Bjørklund

Strandabø

et al. 2018

Toxicology and Applied Pharmacology

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Perfluoroalkyl acids (PFAAs) are persistent compounds used in many industrial as well as consumer products. Despite restrictions, these compounds are found at measurable concentrations in samples of human and animal origin. In the present study we examined whether the effects on cell viability of two sulfonated and four carboxylated PFAAs in cultures of cerebellar granule neurons (CGNs), could be associated with deleterious activation of the N-methyl-d-aspartate receptor (NMDA-R). PFAA-induced effects on viability in rat CGNs and unstimulated PC12 cells were examined using the MTT assay. Cells from the PC12 rat pheochromocytoma cell line lack the expression of functional NMDA-Rs and were used to verify lower toxicity of perfluorooctanesulfonic acid (PFOS) in cells not expressing NMDA-Rs. Protective effects of NMDA-R antagonists, and extracellular as well as intracellular Ca chelators were investigated. Cytosolic Ca ([Ca]) was measured using Fura-2. In rat CGNs the effects of the NMDA-R antagonists MK-801, memantine and CPP indicated involvement of the NMDA-R in the decreased viability induced by PFOS and perfluorohexanesulfonic acid (PFHxS). No effects were associated with the four carboxylated PFAAs studied. Further, EGTA and CPP protected against PFOS-induced decreases in cell viability, whereas no protection was afforded by BAPTA-AM. [Ca] significantly increased after exposure to PFOS, and this increase was completely blocked by MK-801. In PC12 cells a higher concentration of PFOS was required to induce equivalent levels of toxicity as compared to in rat CGNs. PFOS-induced toxicity in PC12 cells was not affected by CPP. In conclusion, PFOS at the tested concentrations induces excitotoxicity in rat CGNs, which likely involves influx of extracellular Ca via the NMDA-R. This effect can be blocked by specific NMDA-R antagonists.

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Section: Discussionmentioning

confidence: 70%

PFOS-induced excitotoxicity is dependent on Ca2+ influx via NMDA receptors in rat cerebellar granule neurons

Berntsen

Bjørklund

Strandabø

et al. 2018

Toxicology and Applied Pharmacology

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“…The mechanism(s) underlying the observed neurotoxicity have been studied in vitro in neuronal cells. At (high) micromolar concentrations, PFOS and/or PFOA can affect a range of (pre)-synaptic processes, including reduction of cell viability [26][27][28][29] , altered neuronal differentiation 30 , increased formation of reactive oxygen species 27,28,[31][32][33][34] , and increased intracellular calcium (Ca 2+ ) concentrations 35,36 . In addition, PFOS and PFOA may also affect postsynaptic processes, including altered glutamate-activated currents and increase of potassium currents 37,38 .…”

mentioning

confidence: 99%

Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) acutely affect human α1β2γ2L GABAA receptor and spontaneous neuronal network function in vitro

Tukker

Bouwman

Kleef

et al. 2020

Sci Rep

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Concerns about the neurotoxic potential of polyfluoroalkyl substances (PFAS) such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) increase, although their neurotoxic mechanisms of action remain debated. Considering the importance of the GABA A receptor in neuronal function, we investigated acute effects of PFAS on this receptor and on spontaneous neuronal network activity. PFOS (Lowest Observed Effect Concentration (LOEC) 0.1 µM) and PFOA (LOEC 1 µM) inhibited the GABA-evoked current and acted as non-competitive human GABA A receptor antagonists. Network activity of rat primary cortical cultures increased following exposure to PFOS (LOEC 100 µM). However, exposure of networks of human induced pluripotent stem cell (hiPSC)-derived neurons decreased neuronal activity. The higher sensitivity of the α 1 β 2 γ 2L GABA A receptor for PFAS as compared to neuronal networks suggests that PFAS have additional mechanisms of action, or that compensatory mechanisms are at play. Differences between rodent and hiPSC-derived neuronal networks highlight the importance of proper model composition. LOECs for PFAS on GABA A receptor and neuronal activity reported here are within or below the range found in blood levels of occupationally exposed humans. For PFOS, LOECs are even within the range found in human serum and plasma of the general population, suggesting a clear neurotoxic risk. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are well-known perfluoroalkyl substances (PFAS) consisting of an eight-carbon chain in which hydrogen atoms have been substituted with fluorine. Their combined hydrophobic, hydrophilic, oleophobic and lipophobic properties make them ideal industrial surfactants for the manufacturing of consumer products, including paint, stain repellents, fire-fighting foams, and non-stick cookware coatings. The strong carbon-fluorine bond renders PFOS and PFOA highly persistent and studies have shown their presence in the environment, wildlife and even human blood (for reviews see 1,2). By 2002, production of PFOS was phased out and production phase out of PFOA followed in 2006 3. Recent studies indicate that these efforts may be responsible for a reduction in human blood levels in some areas, but the long half-lives of PFOS and PFOA result in slow elimination from environment and humans 4,5. Research has demonstrated that the (developing) nervous system is one of the most sensitive targets for PFOS and PFOA. In mice and rats exposed pre-and/or neonatally to PFOS or PFOA, increased motor activity, decreased habituation and deficits in spatial learning and memory abilities have been observed 6-11. Developmental neurotoxicity has also been observed in other species, including chicken 12 and zebrafish larvae 13,14. However, epidemiological studies have been inconclusive on the risks of PFAS exposure on neurodevelopment. Some studies indicate an association between prenatal PFOS and/or PFOA exposure and an increased risk on congenital cerebral palsy 15 , neuro-behavioural developmen...

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“…Perfluorooctane sulfonate (PFOS) and Perfluorooctanoic acid (PFOA) are the most frequently detected PFCs [1]. PFOS has recently been included on the list of restricted-use compounds that appear in Annex B of the Stockholm Convention on Persistent Organic Pollutants, May 2009 [2]. The structure of PFOS and PFOA reflects a high electronegativity of fluorine atoms; the carbon-fluorine bond generates a strong dipole moment [3].…”

Section: Introductionmentioning

confidence: 99%

Method development and initial results of testing for perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in waterproof sunscreens

Keawmanee

Boontanon

2015

Environmental Engineering Research

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Perfluorooctane sulfonate (PFOS) and Perfluorooctanoic acid (PFOA) are persistent environmental pollutants, extremely stable, and possibly adversely affect human health. They are widely used in many industries and consumer goods, including sunscreen products. These substances are stable chemicals made of long carbon chains, having both lipid-and water-repellent qualities. The research objectives are (1) to find the most effective method for the preparation of semi-liquid samples by comparing solid phase extraction (SPE) and centrifugation after Pressurized liquid extraction (PLE), and (2) to determine the contamination levels of PFOS and PFOA in waterproof sunscreen samples. All sunscreen samples were analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Sunscreen samples were purchased from domestic and international brands sold in Thailand. Special chemical properties were considered for the selection of samples, e.g., those found in waterproof, sweat resistant, water resistant, and non-stick products. Considering the factors of physical properties, e.g., operation time, chemical consumption, and recovery percentage for selecting methods to develop, the centrifugation method using 2 mL of extracted sample with the conditions of 12,000 rpm and 5˚C for 1 hour after PLE was chosen. The highest concentrations of PFOS and PFOA were detected at 0.0671 ng/g and 21.0644 ng/g, respectively. Even though present concentrations are found at ng/g levels, the daily use of sunscreen products is normally several grams. Therefore, a risk assessment of PFOS and PFOA contamination in sunscreen products is an important concern, and more attention needs to be paid to the long-term effects on human health.

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Possible mechanism of perfluorooctane sulfonate and perfluorooctanoate on the release of calcium ion from calcium stores in primary cultures of rat hippocampal neurons

Cited by 69 publications

References 52 publications

PFOS-induced excitotoxicity is dependent on Ca2+ influx via NMDA receptors in rat cerebellar granule neurons

PFOS-induced excitotoxicity is dependent on Ca2+ influx via NMDA receptors in rat cerebellar granule neurons

Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) acutely affect human α1β2γ2L GABAA receptor and spontaneous neuronal network function in vitro

Method development and initial results of testing for perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in waterproof sunscreens

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