Acute Enhancement of Synaptic Transmission and Chronic Inhibition of Synaptogenesis Induced by Perfluorooctane Sulfonate through Mediation of Voltage-dependent Calcium Channel
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Perfluorooctane sulfonate (PFOS) is a persistent and bioaccumulative pollutant ubiquitous in wildlife and humans. Although the distribution and fate of PFOS have been widely studied, its potential neurotoxicity remains largely unknown. In the present study, the acute and chronic effects of PFOS on the development and synaptic transmission of hippocampal neurons was examined. Perfusion with PFOS markedly increased the frequency of miniature postsynaptic currents (mPSCs) and slightly elevated the amplitude of mPSCs in cultured hippocampal neurons. Perfusion with PFOS also increased the amplitude of field excitatory postsynaptic potentials (fEPSPs) recorded in the CA1 region of hippocampal slices. Both of these effects were largely blocked by the L-type Ca2+ channel antagonist nifedipine. Further studies showed that PFOS enhanced inward Ca2+ currents and increased intracellular Ca2+ in cultured neurons; these effects were also substantially inhibited by nifedipine. Moreover, prolonged treatment with PFOS moderately inhibited neurite growth and dramatically suppressed synaptogenesis in cultured neurons in a nifedipine-sensitive manner. Thus, through enhancement of Ca2+ channels, PFOS may exhibit both acute excitotoxic effects on synaptic function and chronically inhibit synaptogenesis in the brain.
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PFAS-induced neuronal Ca2+ increases appear to be driven by Ca2+ influx from the extracellular space and intracellular Ca2+ storage organelles such as mitochondria and endoplasmic reticulum.
“appear to be driven by Ca2+ influx from the extracellular space and intracellular Ca2+ storage organelles, such as the mitochondria and endoplasmic reticulum”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Liao et al., 2008
In vitro pharmacological studies have identified the L-type voltage-gated Ca2+ channel, inositol 1,4,5-triphosphate receptor, and ryanodine receptors as mediators of Ca2+ overload in PFAS-exposed neurons.
“in vitro pharmacological studies have identified the L-type voltage-gated Ca2+ channel, inositol 1,4,5-triphosphate receptor, and ryanodine receptors as mediators of Ca2+ overload in PFAS exposed neurons”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Liao et al., 2008
PFAS-induced increases in neuronal Ca2+ have been observed in both in vivo and in vitro studies.
“PFAS-induced increases in neuronal Ca2+ have been observed in both in vivo and in vitro studies”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Liao et al., 2008
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- Authors
- Liao, C.-Y., Li, X.-Y., Wu, B., Duan, S., & Jiang, G.-B.
- Affiliations
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China, and Institute of Neuroscience and Key Laboratory of Neurobiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
- Chinese Academy of Sciences (CN)
- Corresponding author
- Duan, Shumin
- Venue
- Environmental Science & Technology
- Publisher
- American Chemical Society (ACS)
- Published
- 2008-06-18
- Volume
- 42
- Issue
- 14
- Pages
- 5335-5341
- ISSN
- 0013-936X (ISSN-L)
- 1520-5851
- OpenAlex
- W2028689425
- Cited by
- 96
- References
- 34
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 6 · 2023: 8 · 2022: 2 · 2021: 3 · 2020: 9 · 2019: 5 · 2018: 5 · 2017: 4 · 2016: 7 · 2015: 4 · 2014: 3 · 2012: 6
- FWCI
- 3.89
- Type
- journal article
- Language
- en
- Open access
- green
- ir.rcees.ac.cn
- Licence
- cc-by-nc-nd
- Locations
- Environmental Science & Technology (publishedVersion)
- PubMed (publishedVersion)
- Research Center for Eco-Environmental Sciences OpenIR (Chinese Academy of Sciences) (submittedVersion, cc-by-nc-nd)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Keywords
- PFOS, synaptic transmission, synaptogenesis, hippocampal neurons, L-type voltage-dependent calcium channels, nifedipine, miniature postsynaptic currents, excitatory postsynaptic potentials, intracellular calcium, neurite outgrowth, persistent organic pollutants
- MeSH terms
- Animals, Calcium, Calcium Channel Blockers, Cells, Cultured, Fluorocarbons, Hippocampus, Humans, Synaptic Transmission, Neurons, Nifedipine, Synapses, Calcium Channels, Rats, Sprague-Dawley, Alkanesulfonic Acids, Patch-Clamp Techniques, Rats
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