More Signs of Neurotoxicity of Surfactants and Flame Retardants - Neonatal PFOS and PBDE 99 Cause Transcriptional Alterations in Cholinergic Genes in the Mouse CNS
Abstract
Maternally and lactionally transferred persistent organic pollutants may interfere with CNS development. Here, 10-day-old male mice were exposed to single oral doses of PFOS (perflourooctanosulphonate) or PBDE 99 (2,2',4,4',5-penta-bromodiphenyl ether), and examined for changes in cholinergic gene transcription in the CNS 24h and 7 weeks later. 24h after exposure qPCR analyses revealed decreased transcription of nAChR-β2 and AChE in cortex, and increased mAChR-5 in hippocampus of PFOS treated mice. Neonatal PFOS treatment altered spontaneous behaviour at 2 months of age but did not affect gene transcription in adults. At 2 months of age neonatally PBDE 99 treated mice had altered spontaneous behaviour, and cortical transcription of AChE, nAChR-α4, nAChR-β2 and mAChR-5 were elevated. Our results indicate that PFOS and PBDE 99 affects the developing central cholinergic system by altering gene transcription in cortex and hippocampus, which may in part account for mechanisms causing changes in spontaneous behaviour.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Hallgren et al. (2015) found that PFOS decreased transcription of genes encoding proteins essential to cholinergic system functioning in the brain, including acetylcholinesterase (AchE), nicotinic acetylcholine receptor β2 (nAChR-β2), and muscarinic acetylcholine receptor m5 (mAChR-5).
“In conjunction with altered spontaneous motor activity, Hallgren et al. (2015) found that PFOS decreased transcription of genes encoding proteins essential to cholinergic system functioning in the brain, including acetylcholinesterase (AchE), nicotinic acetylcholine receptor β2 (nAChR-β2), and muscarinic acetylcholine receptor m5 (mAChR-5).”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Hallgren et al., 2015
Decreased habituation was observed in mice after exposure to 8.7 mg/kg PFOA or 11.3 mg/kg PFOS, whereas altered spontaneous behavior was observed after exposure to 0.58 mg/kg PFOA or 0.75 mg/kg PFOS.
“Decreased habituation was observed in the mice after exposure to 8.7 mg/kg PFOA or 11.3 mg/kg PFOS, whereas altered spontaneous behavior was observed after exposure to 0.58 mg/kg PFOA or 0.75 mg/kg PFOS (Johansson et al., 2008; Hallgren et al., 2015).”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Hallgren et al., 2015
In inbred male NMRI mice, a single oral exposure of PFOA or PFOS at PND 10 caused a long-lasting hyperactive phenotype at 2 and 4 months of age, characterized by decreased habituation and altered spontaneous behavior.
“In inbred male NMRI mice, a single oral exposure of PFOA or PFOS at PND 10 caused a long-lasting hyperactive phenotype at 2 and 4 months of age, characterized by decreased habituation and altered spontaneous behavior (Johansson et al., 2008; Hallgren et al., 2015).”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Hallgren et al., 2015
PFAS 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 Hallgren et al., 2015
Cites
Comparative aspects of the brain growth spurt
Dobbing, J., & Sands, J. (1979) · Early Human Development · doi:10.1016/0378-3782(79)90022-7 · Cited by 2,506 · see citing works
Developmental neurotoxicity of industrial chemicals
Grandjean, P., & Landrigan, P. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69665-7 · Cited by 1,984 · see citing works
Neuronal nicotinic receptors in the human brain
Paterson, D., & Nordberg, A. K. (2000) · Progress in Neurobiology · doi:10.1016/s0301-0082(99)00045-3 · Cited by 782 · see citing works
Rauh, V. A., Garfinkel, R., Perera, F. P., Andrews, H. F., Hoepner, L., Barr, D. B., Whitehead, R., Tang, D., & Whyatt, R. W. (2006) · Pediatrics · doi:10.1542/peds.2006-0338 · Cited by 734 · see citing works
Neurochemical aspects of the ontogenesis of cholinergic neurons in the rat brain
Coyle, J. T., & Yamamura, H. I. (1976) · Brain Research · doi:10.1016/0006-8993(76)90310-3 · Cited by 732 · see citing works
Neurotransmitter regulation of neuronal outgrowth, plasticity and survival
Lipton, S. A., & Kater, S. B. (1989) · Trends in Neurosciences · doi:10.1016/0166-2236(89)90026-x · Cited by 724 · see citing works
Cognitive functions of cortical acetylcholine: toward a unifying hypothesis
Sarter, M. F., & Bruno, J. P. (1997) · Brain Research Reviews · doi:10.1016/s0165-0173(96)00009-4 · Cited by 662 · see citing works
(1981) · Advances in behavioral biology · doi:10.1007/978-1-4684-8643-8 · Cited by 614 · see citing works
(1969) · Annals of Internal Medicine · doi:10.7326/0003-4819-71-4-883_2 · Cited by 592 · see citing works
Turning of nerve growth cones induced by neurotransmitters
Zheng, J. Q., Felder, M., Connor, J. A., & Poo, M.-M. (1994) · Nature · doi:10.1038/368140a0 · Cited by 580 · see citing works
Nicotine binding and nicotinic receptor subunit RNA after chronic nicotine treatment
Marks, M., Pauly, Jr., Gross, S., Deneris, E., Hermans-Borgmeyer, I., Heinemann, S., & Collins, A. (1992) · The Journal of Neuroscience · doi:10.1523/jneurosci.12-07-02765.1992 · Cited by 551 · see citing works
Exposure to Perfluorooctane Sulfonate during Pregnancy in Rat and Mouse. II: Postnatal Evaluation
Lau, C., Thibodeaux, J. R., Hanson, R. G., Rogers, J. M., Grey, B. E., Stanton, M. E., Butenhoff, J. L., & Stevenson, L. A. (2003) · Toxicological Sciences · doi:10.1093/toxsci/kfg122 · Cited by 549 · see citing works
Kärrman, A., Ericson, I., van Bavel, B., Darnerud, P. O., Aune, M., Glynn, A. W., Lignell, S., & Lindström, G. (2006) · Environmental Health Perspectives · doi:10.1289/ehp.9491 · Cited by 469 · see citing works
Johansson, N., Fredriksson, A., & Eriksson, P. (2008) · NeuroToxicology · doi:10.1016/j.neuro.2007.10.008 · Cited by 463 · see citing works
Self-citationAttention-deficit/hyperactivity disorder and urinary metabolites of organophosphate pesticides
Bouchard, M. F., Bellinger, D. C., Wright, R. O., & Weisskopf, M. G. (2010) · Pediatrics · doi:10.1542/peds.2009-3058 · Cited by 457 · see citing works
Roberts, E. M., English, P. B., Grether, J. K., Windham, G. C., Somberg, L., & Wolff, C. (2007) · Environmental Health Perspectives · doi:10.1289/ehp.10168 · Cited by 442 · see citing works
Nerve Growth Factor Gene Expression in the Developing Rat Brain
Large, T. H., Bodary, S. C., Clegg, D., Weskamp, G., Otten, U., & Reichardt, L. F. (1986) · Science · doi:10.1126/science.3764415 · Cited by 435 · see citing works
Maternal lifestyle and environmental risk factors for autism spectrum disorders
Lyall, K., Schmidt, R. J., & Hertz-Picciotto, I. (2014) · International Journal of Epidemiology · doi:10.1093/ije/dyt282 · Cited by 427 · see citing works
Design and Statistical Methods in Studies Using Animal Models of Development
Festing, M. F. W. (2006) · ILAR Journal · doi:10.1093/ilar.47.1.5 · Cited by 362 · see citing works
Calabresi, P., Picconi, B., Parnetti, L., & Filippo, M. D. (2006) · The Lancet Neurology · doi:10.1016/s1474-4422(06)70600-7 · Cited by 337 · see citing works
Viberg, H. (2003) · Toxicological Sciences · doi:10.1093/toxsci/kfg210 · Cited by 319 · see citing works
Self-citationEriksson, P., Viberg, H., Jakobsson, E., Örn, U., & Fredriksson, A. (2002) · Toxicological Sciences · doi:10.1093/toxsci/67.1.98 · Cited by 318 · see citing works
Self-citationJohansson, N., Eriksson, P., & Viberg, H. (2009) · Toxicological Sciences · doi:10.1093/toxsci/kfp029 · Cited by 284 · see citing works
Self-citationPlasticity in the neocortex: mechanisms underlying recovery from early brain damage
Kolb, B. E., & Whishaw, I. Q. (1989) · Progress in Neurobiology · doi:10.1016/0301-0082(89)90023-3 · Cited by 261 · see citing works
Lazic, S. E., & Essioux, L. (2013) · BMC Neuroscience · doi:10.1186/1471-2202-14-37 · Cited by 247 · see citing works
The cholinergic system and hippocampal plasticity
Drever, B. D., Riedel, G., & Platt, B. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.11.037 · Cited by 240 · see citing works
The expanding role of nerve growth factor: from neurotrophic activity to immunologic diseases
Aloe, L., Bracci‐Laudiero, L., Bonini, S., Manni, L., & Aloe, L. (1997) · Allergy · doi:10.1111/j.1398-9995.1997.tb01247.x · Cited by 228 · see citing works
Developmental Neurotoxicity of Perfluorinated Chemicals Modeled <i>in Vitro</i>
Slotkin, T. A., MacKillop, E. A., Melnick, R. L., Thayer, K. A., & Seidler, F. J. (2008) · Environmental Health Perspectives · doi:10.1289/ehp.11253 · Cited by 225 · see citing works
Li, Y., Holtzman, D. M., Kromer, L., Kaplan, D., Chua-Couzens, J., Clary, D. O., Knüsel, B., & Mobley, W. C. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-04-02888.1995 · Cited by 220 · see citing works
Sternfeld, M., Ming, G., Song, H., Sela, K., Timberg, R., Poo, M.-M., & Soreq, H. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-04-01240.1998 · Cited by 199 · see citing works
Viberg, H., Fredriksson, A., & Eriksson, P. (2002) · Toxicological Sciences · doi:10.1093/toxsci/67.1.104 · Cited by 190 · see citing works
Self-citationLazic, S. E., & Essioux, L. (2016) · Cited by 182 · see citing works
Vulnerable Periods in Developing Brain
Dobbing, J. (1990) · Springer eBooks · doi:10.1007/978-1-4471-1766-7_1 · Cited by 181 · see citing works
She, J., Holden, A., Sharp, M., Tanner, M., Williams-Derry, C., & Hooper, K. (2007) · Chemosphere · doi:10.1016/j.chemosphere.2006.05.154 · Cited by 176 · see citing works
Eriksson, P., Ahlbom, J., & Fredriksson, A. (1992) · Brain Research · doi:10.1016/0006-8993(92)90144-x · Cited by 172 · see citing works
Self-citationAcetylcholine and memory: A long, complex and chaotic but still living relationship
Micheau, J., & Marighetto, A. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.11.052 · Cited by 164 · see citing works
Viberg, H., Fredriksson, A., & Eriksson, P. (2006) · NeuroToxicology · doi:10.1016/j.neuro.2006.08.006 · Cited by 156 · see citing works
Self-citationViberg, H. (2004) · Toxicological Sciences · doi:10.1093/toxsci/kfh215 · Cited by 143 · see citing works
Self-citationRasch, B. H., Born, J., & Gais, S. (2006) · Journal of Cognitive Neuroscience · doi:10.1162/jocn.2006.18.5.793 · Cited by 137 · see citing works
Viberg, H., Mundy, W. R., & Eriksson, P. (2007) · NeuroToxicology · doi:10.1016/j.neuro.2007.10.007 · Cited by 131 · see citing works
Self-citationRao, S., Szabo, D. T., Stoker, T. E., et al. (2011) · Elsevier eBooks · doi:10.1016/b978-0-12-382032-7.10040-2 · Cited by 130 · see citing works
Reproductive and Developmental Toxicology
Hood, R. D., & Parker, R. M. (2010) · Pharmaceutical Sciences Encyclopedia · doi:10.1002/9780470571224.pse080 · Cited by 128 · see citing works
Adult Dose-dependent Behavioral and Cognitive Disturbances after a Single Neonatal PFHxS Dose
Viberg, H., Lee, I., & Eriksson, P. (2013) · Toxicology · doi:10.1016/j.tox.2012.12.013 · Cited by 120 · see citing works
Self-citationFunctional redundancy of acetylcholinesterase and neuroligin in mammalian neuritogenesis
Grifman, M., Galyam, N., Seidman, S., & Soreq, H. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.23.13935 · Cited by 116 · see citing works
Neurotoxicity of Perfluorooctane Sulfonate to Hippocampal Cells in Adult Mice
Long, Y., Wang, Y., Ji, G., Yan, L., Hu, F., & Gu, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054176 · Cited by 106 · see citing works
Postnatal Development of Cholinergic Enzymes and Receptors in Mouse Brain
Fiedler, E. P., Marks, M. J., & Collins, A. C. (1987) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1987.tb00990.x · Cited by 101 · see citing works
Viberg, H., Fredriksson, A., & Eriksson, P. (2004) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2004.02.004 · Cited by 98 · see citing works
Self-citationHuman maternal and umbilical cord blood concentrations of polybrominated diphenyl ethers
Foster, W. G., Gregorovich, S., Morrison, K. M., Atkinson, S. A., Kubwabo, C., Stewart, B., & Teo, K. K. (2011) · Chemosphere · doi:10.1016/j.chemosphere.2011.05.028 · Cited by 96 · see citing works
Eriksson, P., Lundkvist, U., & Fredriksson, A. (1991) · Toxicology · doi:10.1016/0300-483x(91)90150-y · Cited by 95 · see citing works
Self-citationAcetylcholinesterase in cell adhesion, neurite growth and network formation
Sperling, L. E., & Layer, P. G. (2008) · FEBS Journal · doi:10.1111/j.1742-4658.2007.06237.x · Cited by 91 · see citing works
Eriksson, P., & Talts, U. (2000) · PubMed · Cited by 81 · see citing works
Differences in neonatal neurotoxicity of brominated flame retardants, PBDE 99 and TBBPA, in mice
Viberg, H., & Eriksson, P. (2011) · Toxicology · doi:10.1016/j.tox.2011.07.010 · Cited by 79 · see citing works
Self-citationDay, T., & Greenfield, S. A. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00031-3 · Cited by 79 · see citing works
Transcriptional Effects of Prenatal and Neonatal Exposure to PFOS in Developing Rat Brain
Wang, F., Liu, W., Jin, Y., Dai, J., Yu, W., Liu, X., & Liu, L. (2010) · Environmental Science & Technology · doi:10.1021/es902799f · Cited by 77 · see citing works
Umbilical cord blood levels of perfluoroalkyl acids and polybrominated flame retardants.
Arbuckle, T., Kubwabo, C., Walker, M., Davis, K. A., Lalonde, K., Kosarac, I., Wen, S.-W., & Arnold, D. (2013) · International Journal of Hygiene and Environmental Health · doi:10.1016/j.ijheh.2012.03.004 · Cited by 75 · see citing works
Dupree, J. L., & Bigbee, J. W. (1994) · Journal of Neuroscience Research · doi:10.1002/jnr.490390508 · Cited by 71 · see citing works
Lee, I., & Viberg, H. (2013) · NeuroToxicology · doi:10.1016/j.neuro.2013.05.007 · Cited by 69 · see citing works
Self-citationBerlanga, M. L., Simpson, T. K., & Alcantara, A. A. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20684 · Cited by 68 · see citing works
Viberg, H., Fredriksson, A., & Eriksson, P. (2005) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2005.02.004 · Cited by 61 · see citing works
Self-citationHuang, L. Z., & Winzer‐Serhan, U. H. (2006) · Brain Research · doi:10.1016/j.brainres.2006.06.084 · Cited by 52 · see citing works
Berse, B., López-Coviella, I., & Blusztajn, J. K. (1999) · Biochemical Journal · doi:10.1042/bj3420301 · Cited by 50 · see citing works
Wang, F., Liu, W., Jin, Y., Dai, J., Zhao, H., Xie, Q. L., Liu, X., Yu, W., & Ma, J. (2011) · Toxicological Sciences · doi:10.1093/toxsci/kfr068 · Cited by 50 · see citing works
Sand, S. (2004) · Toxicological Sciences · doi:10.1093/toxsci/kfh222 · Cited by 49 · see citing works
Eriksson, P. E., Archer, T., & Fredriksson, A. (1990) · Brain Research · doi:10.1016/0006-8993(90)90446-i · Cited by 45 · see citing works
Self-citationBuratovic, S., Viberg, H., Fredriksson, A., & Eriksson, P. (2014) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2014.08.010 · Cited by 43 · see citing works
Self-citationViberg, H., & Lee, I. (2012) · NeuroToxicology · doi:10.1016/j.neuro.2012.09.002 · Cited by 43 · see citing works
Self-citationSperling, L. E., Klaczinski, J., Schütz, C., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036683 · Cited by 33 · see citing works
Llansola, M., Erceg, S., Monfort, P., et al. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05289.x · Cited by 31 · see citing works
Acetylcholine influences growth cone motility and morphology of developing thalamic axons
Rüdiger, T., & Bolz, J. (2008) · Cell Adhesion & Migration · doi:10.4161/cam.2.1.5909 · Cited by 25 · see citing works
Decker, M. W., & Majchrzak, M. J. (1993) · Behavioral and Neural Biology · doi:10.1016/0163-1047(93)90271-i · Cited by 21 · see citing works
Tiered testing in mammals - the neonatal animal model
Eriksson, P. O., & Viberg, H. (2005) · Cited by 15 · see citing works
Self-citationScience for a safe chemical environment
Hansson, S. O., & Rudén, C. (2005) · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Starnes, H. M., Rock, K. D., Jackson, T. W., & Belcher, S. M. (2022) · Frontiers in Toxicology · doi:10.3389/ftox.2022.881584 · Cited by 166 · see citing works
Brown-Leung, J. M., & Cannon, J. R. (2022) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.2c00072 · Cited by 164 · see citing works
Perfluoroalkyl Chemicals in Neurological Health and Disease: Human Concerns and Animal Models
Piekarski, D., Diaz, K., & McNerney, M. (2020) · NeuroToxicology · doi:10.1016/j.neuro.2020.01.001 · Cited by 76 · see citing works
Yuan, Z., Shao, X., Miao, Z., Zhao, B., Zheng, Z., & Zhang, J. (2018) · Chemosphere · doi:10.1016/j.chemosphere.2018.05.011 · Cited by 64 · see citing works
Li, S., Qin, S., Zeng, H., Chou, W., Oudin, A., Kanninen, K. M., Jalava, P., Dong, G., & Zeng, X. (2024) · Eco-Environment & Health · doi:10.1016/j.eehl.2024.08.002 · Cited by 54 · see citing works
Khezri, A., Fraser, T., Nourizadeh-Lillabadi, R., Kamstra, J., Berg, V., Zimmer, K., & Ropstad, E. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18020291 · Cited by 47 · see citing works
- Authors
- Hallgren, S., Fredriksson, A., & Viberg, H.
- Affiliations
- Uppsala University (SE)
- Corresponding author
- Hallgren, Stefan
- Venue
- Environmental Toxicology and Pharmacology
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 40
- Issue
- 2
- Pages
- 409-416
- ISSN
- 1382-6689 (ISSN-L)
- OpenAlex
- W776193939
- Cited by
- 48
- References
- 72
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 4 · 2023: 8 · 2022: 8 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 1 · 2015: 1
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Environmental Toxicology and Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Uppsala Universitet
- 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 › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
- Keywords
- PFOS, PBDE-99, perfluorinated surfactants, brominated flame retardants, neurotoxicity, cholinergic system, gene transcription, Ache, hippocampus, cerebral cortex, central nervous system development, persistent organic pollutants, spontaneous behavior, neonatal exposure
- MeSH terms
- Acetylcholinesterase, Animals, Animals, Newborn, Behavior, Animal, Brain, Flame Retardants, Fluorocarbons, Male, Receptors, Nicotinic, Gene Expression, Alkanesulfonic Acids, Gene Expression Regulation, Developmental, Receptor, Muscarinic M5, Mice, Halogenated Diphenyl Ethers, GPI-Linked Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
