Neurotoxicity of Perfluorooctane Sulfonate to Hippocampal Cells in Adult Mice
Open accessAbstract
Perfluorooctane sulfonate (PFOS) is a ubiquitous pollutant and found in the environment and in biota. The neurotoxicity of PFOS has received much concern among its various toxic effects when given during developing period of brain. However, little is known about the neurotoxic effects and potential mechanisms of PFOS in the mature brain. Our study demonstrated the neurotoxicity and the potential mechanisms of PFOS in the hippocampus of adult mice for the first time. The impairments of spatial learning and memory were observed by water maze studies after exposure to PFOS for three months. Significant apoptosis was found in hippocampal cells after PFOS exposure, accompanied with a increase of glutamate in the hippocampus and decreases of dopamine (DA) and 3,4-dihydrophenylacetic acid (DOPAC) in Caudate Putamen in the 10.75 mg/kg PFOS group. By two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) analysis, seven related proteins in the hippocampus that responded to PFOS exposure were identified, among which, Mib1 protein (an E3 ubiquitin-protein ligase), Herc5 (hect domain and RLD 5 isoform 2) and Tyro3 (TYRO3 protein tyrosine kinase 3) were found down-regulated, while Sdha (Succinate dehydrogenase flavoprotein subunit), Gzma (Isoform HF1 of Granzyme A precursor), Plau (Urokinase-type plasminogen activator precursor) and Lig4 (DNA ligase 4) were found up-regulated in the 10.75 mg/kg PFOS-treated group compare with control group. Furthermore, we also found that (i) increased expression of caspase-3 protein and decreased expression of Bcl-2, Bcl-XL and survivin proteins, (ii) the increased glutamate release in the hippocampus. All these might contribute to the dysfunction of hippocampus which finally account for the impairments of spatial learning and memory in adult mice.
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Long et al. (2013) found that mice exposed to 0.43, 2.15, or 10.75 mg/kg PFOS daily for 3 months showed a dose-dependent impairment in spatial and learning memory.
“Long et al. (2013) exposed animals to 0.43, 2.15, or 10.75 mg/kg PFOS daily for 3 months, and also noted a dose-dependent impairment in spatial and learning memory.”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Long et al., 2013
The Materials and Methods section confirms that adult mice received 0.43, 2.15, or 10.75 mg/kg PFOS daily for three months. The Results section reports impaired spatial learning and memory at 2.15 and 10.75 mg/kg, but does not report significant impairment at 0.43 mg/kg or establish a dose-dependent effect across all three doses. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThere are inconsistencies in the literature regarding the direction of change for dopamine levels with PFAS exposure, with dopamine increasing in some studies and decreasing in others.
“There are inconsistencies in the literature regarding the direction of change for dopamine levels with dopamine increasing with PFAS exposure in some studies and decreasing in others”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Long et al., 2013
The Results section ('Levels of Neurotrasmitters in Caudate Putamen and Hippocampus'; page unavailable) reports significantly decreased dopamine in the caudate putamen of adult mice at the highest PFOS dose. Our copy does not report studies finding increased dopamine after PFAS exposure or describe an inconsistency across studies, so it supports only the decrease side of the claim. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPFAS exposure has been shown to disrupt glutamate, GABA, dopamine, acetylcholine, and serotonin levels.
“PFAS exposure has been shown to disrupt glutamate, γ-aminobutyric acid (GABA), dopamine, acetylcholine, and serotonin levels”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Long et al., 2013
The Results section (page unavailable) reports significantly increased hippocampal glutamate and decreased caudate-putamen dopamine after high-dose PFOS exposure in adult mice. It reports only a slight, nonsignificant GABA increase and does not report acetylcholine or serotonin levels. The claim therefore extends beyond the neurotransmitter changes demonstrated in this study. (LLM, conf=0.90)
Experimental — accuracy not yet measuredExposure to PFOS has been associated with deficits in spatial learning and memory in a Morris Water Maze task in adult mice.
“Exposure to PFOS has been associated with deficits in spatial learning and memory in a Morris Water Maze task in adult mice (Fuentes et al., 2007b; Long et al., 2013).”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Long et al., 2013
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- Authors
- Long, Y., Wang, Y., Ji, G., Yan, L., Hu, F., & Gu, A.
- Affiliations
- China Pharmaceutical University (CN)
- Nanjing Medical University (CN)
- Ministry of Ecology and Environment (CN)
- State Key Laboratory of Reproductive Medicine (CN)
- Corresponding author
- Gu, Aihua
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-01-30
- Volume
- 8
- Issue
- 1
- Pages
- e54176
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3559704
- OpenAlex
- W2070928735
- Cited by
- 106
- References
- 32
- Citations by year
- 2026: 12 · 2025: 9 · 2024: 15 · 2023: 11 · 2022: 8 · 2021: 7 · 2020: 7 · 2019: 5 · 2018: 6 · 2017: 3 · 2016: 5 · 2015: 10 · 2014: 4 · 2013: 4
- FWCI
- 6.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Natural Science Foundation of China (81172694, 30901210)
- Government of Jiangsu Province
- Natural Science Foundation of Jiangsu Province
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Keywords
- PFOS, hippocampal neurons, apoptosis, spatial learning and memory impairment, glutamate release, dopamine, caudate-putamen, MIB-1, HERC5, Tyro3, caspase-3, Bcl-2 family proteins, survivin, ubiquitin-proteasome system, protein expression profiling, perfluorinated compounds
- MeSH terms
- Animals, Dopamine, Fluorocarbons, Gene Expression Regulation, Hippocampus, Memory, 3,4-Dihydroxyphenylacetic Acid, Apoptosis, Alkanesulfonic Acids, Glutamic Acid, Maze Learning, Mice, Caspase 3
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