PFOS Induces Behavioral Alterations, Including Spontaneous Hyperactivity that Is Corrected by Dexamfetamine in Zebrafish Larvae

Spulber, Stefan; Kilian, Pascal; Wan Ibrahim, Wan Norhamidah; Onishchenko, Natalia; Ulhaq, Mazhar; Norrgren, Leif; Negri, Sara; Di Tuccio, Marcello; Ceccatelli, Sandra

doi:10.1371/journal.pone.0094227

Cited by 98Per- and polyfluoroalkyl substances researchZebrafish Biomedical Research ApplicationsToxic Organic Pollutants Impact

PFOS Induces Behavioral Alterations, Including Spontaneous Hyperactivity that Is Corrected by Dexamfetamine in Zebrafish Larvae

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Spulber, Stefan, Kilian, Pascal, Wan Ibrahim, Wan Norhamidah, Onishchenko, Natalia, Ulhaq, Mazhar, Norrgren, Leif, Negri, Sara, Di Tuccio, Marcello +1 more·2014·PLoS ONE

DOI 10.1371/journal.pone.0094227PMC PMC3989208

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Abstract

Perfluorooctane sulfonate (PFOS) is a widely spread environmental contaminant. It accumulates in the brain and has potential neurotoxic effects. The exposure to PFOS has been associated with higher impulsivity and increased ADHD prevalence. We investigated the effects of developmental exposure to PFOS in zebrafish larvae, focusing on the modulation of activity by the dopaminergic system. We exposed zebrafish embryos to 0.1 or 1 mg/L PFOS (0.186 or 1.858 µM, respectively) and assessed swimming activity at 6 dpf. We analyzed the structure of spontaneous activity, the hyperactivity and the habituation during a brief dark period (visual motor response), and the vibrational startle response. The findings in zebrafish larvae were compared with historical data from 3 months old male mice exposed to 0.3 or 3 mg/kg/day PFOS throughout gestation. Finally, we investigated the effects of dexamfetamine on the alterations in spontaneous activity and startle response in zebrafish larvae. We found that zebrafish larvae exposed to 0.1 mg/L PFOS habituate faster than controls during a dark pulse, while the larvae exposed to 1 mg/L PFOS display a disorganized pattern of spontaneous activity and persistent hyperactivity. Similarly, mice exposed to 0.3 mg/kg/day PFOS habituated faster than controls to a new environment, while mice exposed to 3 mg/kg/day PFOS displayed more intense and disorganized spontaneous activity. Dexamfetamine partly corrected the hyperactive phenotype in zebrafish larvae. In conclusion, developmental exposure to PFOS in zebrafish induces spontaneous hyperactivity mediated by a dopaminergic deficit, which can be partially reversed by dexamfetamine in zebrafish larvae.

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Multiple studies reported that exposure to PFAS induced bouts of hyperactivity but decreased overall locomotion and distance traveled.
“Notably, multiple studies reported that exposure to PFAS induced bouts of hyperactivity, but decreased overall locomotion and distance traveled (Spulber et al., 2014; Jantzen et al., 2016).”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Spulber et al., 2014
In Results (‘Alterations in the pattern of spontaneous activity’; page unavailable), larvae exposed to 1 mg/L PFOS had less frequent but more intense bouts, with greater distance moved within each bout. The Results on visual motor response report lower total distance during a 10-minute dark pulse only at 0.1 mg/L, a dose that did not alter spontaneous bouts. Thus, this paper supports both observations, but not their combination as a single exposure pattern or a general decrease in overall locomotion. (LLM, conf=0.86)
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Background
Assessing the human health risks of perfluorooctane sulfonate by in vivo and in vitro studies
Zeng, Z., Song, B., Xiao, R., Zeng, G., Gong, J., Chen, M., Xu, P., Zhang, P., Shen, M., & Yi, H. (2019) · Environment International · doi:10.1016/j.envint.2019.03.002 · Cited by 297 · see citing works
Molecular psychiatry of zebrafish
Stewart, A. M., Ullmann, J. F. P., Norton, W., Parker, M. O., Brennan, C. H., Gerlai, R. T., & Kalueff, A. V. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.128 · Cited by 229 · see citing works
Assessing the Human Health Risks of Per- and Polyfluoroalkyl Substances: A Need for Greater Focus on Their Interactions as Mixtures
Ojo, A. F., Peng, C., & Ng, J. C. (2021) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2020.124863 · Cited by 221 · see citing works
A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior
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
“While studies on PFAS exposure in adult animals have not reported altered motor activity, several compounds have been shown to elicit developmental impairment of motor activity in mice, rats, and zebrafish (Johansson et al., 2008; Butenhoff et al., 2009b; Huang et al., 2010; Wang M. et al., 2011; Chen et al., 2013; Sp…”
Background
Neurotransmission targets of per-and polyfluoroalkyl substance neurotoxicity: Mechanisms and potential implications for adverse neurological outcomes
Brown-Leung, J. M., & Cannon, J. R. (2022) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.2c00072 · Cited by 164 · see citing works
Behavioural effects and bioconcentration of per- and polyfluoroalkyl substances (PFASs) in zebrafish (Danio rerio) embryos
Menger, F., Pohl, J., Ahrens, L., Carlsson, G., & Örn, S. (2019) · Chemosphere · doi:10.1016/j.chemosphere.2019.125573 · Cited by 155 · see citing works
Zebrafish Models of Neurodevelopmental Disorders: Limitations and Benefits of Current Tools and Techniques
Vaz, R., Hofmeister, W., & Lindstrand, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20061296 · Cited by 143 · see citing works
“In this study, exposure to dexamfetamine, a catecholamine reuptake inhibitor, was able to partially rescue the phenotypes, such as spontaneous swimming [142].”
Background
Comparability of behavioural assays using zebrafish larvae to assess neurotoxicity
Legradi, J., Abdellaoui, N., van Pomeren, M., & Legler, J. (2014) · Environmental Science and Pollution Research · doi:10.1007/s11356-014-3805-8 · Cited by 137 · see citing works
PFOS, PFNA, and PFOA sub-lethal exposure to embryonic zebrafish have different toxicity profiles in terms of morphometrics, behavior and gene expression
Jantzen, C. E., Annunziato, K. A., Bugel, S. M., & Cooper, K. R. (2016) · Aquatic Toxicology · doi:10.1016/j.aquatox.2016.03.026 · Cited by 131 · see citing works
“All three PFC exposures resulted in an increase in swimming activity at 14 dpf, which correlates to previous studies indicating hyperactivity in zebrafish larvae exposed to PFOS (Spulber et al. 2014).”
Result
Bioconcentration and Metabolic Effects of Emerging PFOS Alternatives in Developing Zebrafish
Tu, W., Martínez, R., Navarro‐Martín, L., Kostyniuk, D. J., Hum, C., Huang, J., Deng, M., Jin, Y., Chan, H. M., & Mennigen, J. A. (2019) · Environmental Science & Technology · doi:10.1021/acs.est.9b03820 · Cited by 131 · see citing works
Behavioral, Morphometric, and Gene Expression Effects in Adult Zebrafish (Danio rerio) Embryonically Exposed to PFOA, PFOS, and PFNA
Jantzen, C. E., Annunziato, K. M., & Cooper, K. R. (2016) · Aquatic Toxicology · doi:10.1016/j.aquatox.2016.09.011 · Cited by 113 · see citing works
“Similar observations have been made in mammalian studies, in which exposure to PFOS in mice (0.3 mg/kg/day) induced spontaneous hyperactivity (Spulber et al., 2014) and mice exposed to 0.3 mg/kg PFOA showed changes in exploratory behavior (Onishchenko et al., 2011).”
BackgroundResultInfluential
Thyroid disrupting effects of halogenated and next generation chemicals on the swim bladder development of zebrafish
Godfrey, A., Hooser, B., Abdelmoneim, A., Horzmann, K. A., Freeman, J. L., & Sepúlveda, M. S. (2017) · Aquatic Toxicology · doi:10.1016/j.aquatox.2017.10.024 · Cited by 95 · see citing works
Sex-specific Enhanced Behavioral Toxicity Induced by Maternal Exposure to a Mixture of Low Dose Endocrine-Disrupting Chemicals
Sobolewski, M., Conrad, K., Allen, J. L., Weston, H., Martin, K., Lawrence, B. P., & Cory-Slechta, D. A. (2014) · NeuroToxicology · doi:10.1016/j.neuro.2014.09.008 · Cited by 91 · see citing works
Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) acutely affect human α1β2γ2L GABAA receptor and spontaneous neuronal network function in vitro
Tukker, A. M., Bouwman, L. M. S., van Kleef, R. G. D. M., Hendriks, H. S., Legler, J., & Westerink, R. H. S. (2020) · Scientific Reports · doi:10.1038/s41598-020-62152-2 · Cited by 92 · see citing works
Perfluorooctane sulfonate disrupts the blood brain barrier through the crosstalk between endothelial cells and astrocytes in mice
Yu, Y., Wang, C., Zhang, X., Zhu, J., Wang, L., Ji, M., Zhang, Z., Ji, X., & Wang, S. (2019) · Environmental Pollution · doi:10.1016/j.envpol.2019.113429 · Cited by 85 · see citing works
Differential Developmental Neurotoxicity and Tissue Uptake of the Per- and Polyfluoroalkyl Substance Alternatives, GenX and PFBS
Wasel, O., King, H., Choi, Y. J., Lee, L., & Freeman, J. L. (2023) · Environmental Science & Technology · doi:10.1021/acs.est.3c05023 · Cited by 83 · see citing works
“17,18,56 Dopamine concentration in zebrafish eleuthero-embryos was increased in the 40 ppb GenX exposed group (13% increase, p 0.05, Figure 4A).”
Influential
Unravelling the mechanisms of PFOS toxicity by combining morphological and transcriptomic analyses in zebrafish embryos
Martínez, R., Navarro‐Martín, L., Luccarelli, C., Esteve‐Codina, A., Raldúa, D., Barata, C., Tauler, R., & Piña, B. (2019) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2019.04.200 · Cited by 78 · see citing works
Evaluation of Per- and Polyfluoroalkyl Substances (PFAS) In Vitro Toxicity Testing for Developmental Neurotoxicity
Carstens, K. E., Freudenrich, T. M., Wallace, K., Choo, S., Carpenter, A., Smeltz, M. G., Clifton, M. S., Henderson, W. M., Richard, A. M., Patlewicz, G. Y., et al. (2023) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.2c00344 · Cited by 82 · see citing works
Prenatal perfluoroalkyl substance exposure and neuropsychological development throughout childhood: The INMA Project
Carrizosa, C., Murcia, M., Ballesteros, V., Costa, O., Manzano-Salgado, C. B., Ibarluzea, J. M., Íñiguez, C., Casas, M., Andiarena, A., Llop, S., et al. (2021) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2021.125185 · Cited by 68 · see citing works
Modelling Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) Using Mice and Zebrafish
Dougnon, G., & Matsui, H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23147550 · Cited by 71 · see citing works
Comparative behavioral toxicology with two common larval fish models: Exploring relationships among modes of action and locomotor responses
Steele, W. B., Kristofco, L. A., Corrales, J., Saari, G. N., Haddad, S. P., Gallagher, E. P., Kavanagh, T. J., Kostal, J., Zimmerman, J. B., Voutchkova‐Kostal, A. M., et al. (2018) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2018.05.402 · Cited by 70 · see citing works
Per- and Polyfluoroalkyl Substances (PFAS) Neurotoxicity in Sentinel and Non-Traditional Laboratory Model Systems: Potential Utility in Predicting Adverse Outcomes in Human Health
Foguth, R. M., Sepúlveda, M. S., & Cannon, J. R. (2020) · Toxics · doi:10.3390/toxics8020042 · Cited by 67 · see citing works
“Interestingly, these effects were also rescued with exposure to dexamphetamine, quinpirole, or SKF-81297 [38].”
BackgroundInfluential
Multi- and Transgenerational Effects of Developmental Exposure to Environmental Levels of PFAS and PFAS Mixture in Zebrafish (Danio rerio)
Haimbaugh, A. S., Wu, C., Akemann, C., Meyer, D. N., Connell, M. L., Abdi, M., Khalaf, A., Johnson, D., & Baker, T. R. (2022) · Toxics · doi:10.3390/toxics10060334 · Cited by 66 · see citing works
“Other studies have observed a decreased ratio following F0 PFOS exposure [34].”
Background
Effects of PFOS, F-53B and OBS on locomotor behaviour, the dopaminergic system and mitochondrial function in developing zebrafish (Danio rerio)
Kalyn, M., Lee, H., Curry, J., Tu, W., Ekker, M., & Mennigen, J. A. (2023) · Environmental Pollution · doi:10.1016/j.envpol.2023.121479 · Cited by 61 · see citing works
Neurotoxic effects of perfluoroalkyl acids: Neurobehavioral deficit and its molecular mechanism
Wang, Y., Wang, L., Chang, W., Zhang, Y., Zhang, Y., & Liu, W. (2019) · Toxicology Letters · doi:10.1016/j.toxlet.2019.01.012 · Cited by 60 · see citing works
Long-term consequences of prenatal stress and neurotoxicants exposure on neurodevelopment
Antonelli, M. C., Pallarés, M. E., Ceccatelli, S., & Spulber, S. D. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.05.005 · Cited by 60 · see citing works
“The hyperactive phenotype we observed in zebrafish larvae exposed to the 10 mg/L PFOS – both spontaneous and acoustic startle-induced hyperactivity – was reversed by acute administration of dexamfetamine (Spulber et al., 2014) in a monotonic dose-dependent fashion.”
Developmental exposures to perfluorooctanesulfonic acid (PFOS) impact embryonic nutrition, pancreatic morphology, and adiposity in the zebrafish, Danio rerio
Sant, K. E., Annunziato, K. M., Conlin, S. M., Teicher, G., Chen, P. B., Venezia, O. L., Downes, G. B., Park, Y., & Timme‐Laragy, A. R. (2021) · Environmental Pollution · doi:10.1016/j.envpol.2021.116644 · Cited by 57 · see citing works
“Several kinematic studies in zebra ﬁ sh embryos have previously found increased hyperactivity in PFOS-exposed zebra ﬁ sh embryos and eleutherolarvae (Gaballah et al., 2020; Huang et al., 2010; Khezri et al., 2017; Menger et al., 2020; Spulber et al., 2014).”
Background
Tissue uptake, distribution and elimination of 14C-PFOA in zebrafish (Danio rerio)
Ulhaq, M., Sundström, M., Larsson, P., Gabrielsson, J., Bergman, Å., Norrgren, L., & Örn, S. (2015) · Aquatic Toxicology · doi:10.1016/j.aquatox.2015.04.003 · Cited by 57 · see citing works
“n laboratory studies with zebrafish, behavioral alterations includng spontaneous hyperactivity has been observed after exposure to FOS (Spulber et al., 2014).”
Background
Adverse Outcome Pathway for the Neurotoxicity of Per- and Polyfluoroalkyl Substances: A Systematic Review
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
Zebrafish models for attention deficit hyperactivity disorder (ADHD)
Fontana, B. D., Franscescon, F., Rosemberg, D. B., Norton, W., Kalueff, A. V., & Parker, M. O. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.02.009 · Cited by 47 · see citing works
A Mixture of Persistent Organic Pollutants and Perfluorooctanesulfonic Acid Induces Similar Behavioural Responses, but Different Gene Expression Profiles in Zebrafish Larvae
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
“Similarly, mice exposed to 3 mg/kg/day PFOS displayed spontaneous activity [27] whereas other rodent studies have found that PFOS decreases locomotor activity [48,49].”
BackgroundInfluential
Calcium signaling as a possible mechanism behind increased locomotor response in zebrafish larvae exposed to a human relevant persistent organic pollutant mixture or PFOS
Christou, M., Fraser, T. W. K., Berg, V., Ropstad, E., & Kamstra, J. H. (2020) · Environmental Research · doi:10.1016/j.envres.2020.109702 · Cited by 47 · see citing works
Developmental toxicity of the common UV filter, benophenone-2, in zebrafish embryos.
Fong, H. H., Ho, J. C., Cheung, A., Lai, K., & Tse, W. K. (2016) · Chemosphere · doi:10.1016/j.chemosphere.2016.08.073 · Cited by 42 · see citing works
Are “liquid plastics” a new environmental threat? The case of polyvinyl alcohol
Nigro, L., Magni, S., Ortenzi, M. A., Gazzotti, S., Torre, C. D., & Binelli, A. (2022) · Aquatic Toxicology · doi:10.1016/j.aquatox.2022.106200 · Cited by 46 · see citing works
Association of Prenatal Exposure to Perfluorinated and Polyfluoroalkyl Substances with Childhood Neurodevelopment: A Systematic Review and Meta-Analysis
Liu, D., Yan, S., Liu, Y., Chen, Q., & Ren, S. (2024) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2024.115939 · Cited by 44 · see citing works
Evaluation of the neurotoxic effects of chronic embryonic exposure with inorganic mercury on motor and anxiety-like responses in zebrafish (Danio rerio) larvae
Bakar, N. A., Sata, N. S. A. M., Ramlan, N. F., Ibrahim, W. N. W., Zulkifli, S. Z., Abdullah, C. A. C., Ahmad, S., & Azmai, M. N. A. (2016) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2016.11.008 · Cited by 44 · see citing works
Scale-up approach for supercritical fluid extraction with ethanol–water modified carbon dioxide on Phyllanthus niruri for safe enriched herbal extracts
Hassim, N., Markom, M., Rosli, M. I., & Harun, S. (2021) · Scientific Reports · doi:10.1038/s41598-021-95222-0 · Cited by 43 · see citing works
Cerebral concentration and toxicity of endocrine disrupting chemicals: The implication of blood-brain interfaces
Denuzière, A., & Ghersi‐Egea, J. (2022) · NeuroToxicology · doi:10.1016/j.neuro.2022.04.004 · Cited by 43 · see citing works
Perfluorooctane Sulfonic Acid (Pfos) Exposures Interfere Behaviors and Transcriptions of Genes on Nervous and Muscle System in Zebrafish Embryos
Wang, X., Shi, X., Zheng, S., Zhang, Q., Peng, J., Tan, W., & Wu, K. (2022) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2022.157816 · Cited by 42 · see citing works
Automated, high‐throughput, in vivo analysis of visual function using the zebrafish
Scott, C. A., Marsden, A. N., & Slusarski, D. C. (2016) · Developmental Dynamics · doi:10.1002/dvdy.24398 · Cited by 41 · see citing works
“Some visual assays, such as the VMR, have been successfully automated (Zhang et al., 2012; Gao et al., 2014; Spulber et al., 2014).”
Method
Neurodevelopmental and Metabolomic Responses from Prenatal Coexposure to Perfluorooctanesulfonate (PFOS) and Methylmercury (MeHg) in Sprague-Dawley Rats
Reardon, A. J. F., Karathra, J., Ribbenstedt, A., Benskin, J. P., MacDonald, A. M., Kinniburgh, D. W., Hamilton, T. J., Fouad, K., & Martin, J. W. (2019) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.9b00192 · Cited by 40 · see citing works
ROS-mediated JNK pathway critically contributes to PFOS-triggered apoptosis in SH-SY5Y cells
Sun, P., Gu, L., Luo, J., Qin, Y., Sun, L., & Jiang, S. (2019) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2019.106821 · Cited by 39 · see citing works
An optimized method to assess ototoxic effects in the lateral line of zebrafish (Danio rerio) embryos
Stengel, D., Zindler, F., & Braunbeck, T. A. (2016) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cbpc.2016.11.001 · Cited by 35 · see citing works
“In neurotoxicity, modes of action for PFOS still appear inconclusive (Mariussen, 2012): In larval fish, PFOS disrupts normal behavior (Chen et al., 2013; Spulber et al., 2014; Ulhaq et al., 2013b) indicating effects on neural systems.”
Background
The neurotoxic effect of lactational PFOS exposure on cerebellar functional development in male mice
Ninomiya, A., Mshaty, A., Haijima, A., Yajima, H., Kokubo, M., Khairinisa, M. A., Ariyani, W., Fujiwara, Y., Ishii, S., Hosoi, N., et al. (2021) · Food and Chemical Toxicology · doi:10.1016/j.fct.2021.112751 · Cited by 35 · see citing works
Fetal toxicology
van de Bor, M. (2019) · Handbook of clinical neurology · doi:10.1016/b978-0-444-64029-1.00002-3 · Cited by 33 · see citing works
Analysis of behavioral changes in zebrafish (Danio rerio) larvae caused by aminoglycoside-induced damage to the lateral line and muscles
Han, E., Oh, K. H., Park, S., Rah, Y. C., Park, H., Koun, S., & Choi, J. (2020) · NeuroToxicology · doi:10.1016/j.neuro.2020.03.005 · Cited by 29 · see citing works
Prenatal Exposure to Perfluoroalkyl Substances and Cognitive and Neurobehavioral Development in Children at 6 Years of Age
Xie, Z., Liang, H., Miao, M., Wang, Z., Chen, Y., Yang, L., Zhou, Y., Cao, W., & Yuan, W. (2023) · Environmental Science & Technology · doi:10.1021/acs.est.2c06535 · Cited by 28 · see citing works
Methylmercury interferes with glucocorticoid receptor: Potential role in the mediation of developmental neurotoxicity
Spulber, S. D., Raciti, M., Dulko-Smith, B., Lupu, D., Rüegg, J., Nam, K., & Ceccatelli, S. (2018) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2018.02.021 · Cited by 25 · see citing works
Perfluorooctane sulfonate exposure alters sexual behaviors and transcriptions of genes in hypothalamic–pituitary–gonadal–liver axis of male zebrafish (Danio rerio)
Bao, M., Zheng, S., Liu, C., Huang, W., Xiao, J., & Wu, K. (2020) · Environmental Pollution · doi:10.1016/j.envpol.2020.115585 · Cited by 25 · see citing works
Embryonic exposure to PFAS causes long-term, compound-specific behavioral alterations in zebrafish
Hawkey, A. B., Mead, M., Natarajan, S., Gondal, A., Jarrett, O., & Levin, E. D. (2023) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2023.107165 · Cited by 25 · see citing works
Alterations in circadian entrainment precede the onset of depression-like behavior that does not respond to fluoxetine
Spulber, S. D., Conti, M., DuPont, C. M., Raciti, M., Bose, R. K., Onishchenko, N. R., & Ceccatelli, S. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.94 · Cited by 25 · see citing works
Behavior, metabolism and swimming physiology in juvenile Spinibarbus sinensis exposed to PFOS under different temperatures
Xia, J., Nie, L.-J., Mi, X.-M., Wang, W., Ma, Y., Cao, Z., & Fu, S. (2015) · Fish Physiology and Biochemistry · doi:10.1007/s10695-015-0086-1 · Cited by 24 · see citing works
Perfluorooctanesulfonic acid exposure altered hypothalamic metabolism and disturbed male fecundity
Li, Z., Lin, Z., Ji, S., Lai, K. P., Wan, H., Wong, C. K. C., & Li, L. (2022) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2022.156881 · Cited by 23 · see citing works
Toxicokinetic Modeling of Per- and Polyfluoroalkyl Substance Concentrations within Developing Zebrafish (Danio rerio) Populations
Warner, R. M., Sweeney, L. M., Hayhurst, B. A., & Mayo, M. L. (2022) · Environmental Science & Technology · doi:10.1021/acs.est.2c02942 · Cited by 23 · see citing works
Establishment of a behavioral model to study effects of typical chemicals toward zebrafish larvae
Yuan, S., Tong, W., Zheng, T., Xiaohui, Z., Tang, B., Dang, Y., Letcher, R. J., & Liu, C. (2022) · Hygiene and Environmental Health Advances · doi:10.1016/j.heha.2022.100021 · Cited by 18 · see citing works
Associations of prenatal exposure to per- and polyfluoroalkyl substances (PFAS) with measures of cognition in 7.5-month-old infants: An exploratory study
Enright, E. A., Eick, S. M., Morello-Frosch, R. A., Aguiar, A., Woodbury, M., Sprowles, J. L. N., Geiger, S. D., Trowbridge, J., Andrade, A., Smith, S. C., et al. (2023) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2023.107182 · Cited by 17 · see citing works
Environmental Deterioration Due to Existing and Emerging Persistent Organic Pollutants: An Overview
Harikrishnan, T., & Gopalakrishnan, S. (2021) · Emerging contaminants and associated treatment technologies · doi:10.1007/978-3-030-72441-2_3 · Cited by 15 · see citing works
Loss of ctnnd2b affects neuronal differentiation and behavior in zebrafish
Vaz, R., Edwards, S. J., Rey, A. D., Hofmeister, W., & Lindstrand, A. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1205653 · Cited by 13 · see citing works
The translational genetics of ADHD and related phenotypes in model organisms
Cabana‐Domínguez, J., Antón-Galindo, E., Fernàndez‐Castillo, N., Singgih, E. L., O’Leary, A., Norton, W., Strekalova, T. V., Schenck, A., Reif, A., Lesch, K., et al. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104949 · Cited by 13 · see citing works
PBTK modeled perfluoroalkyl acid kinetics in zebrafish eleutheroembryos suggests impacts on bioconcentrations by chorion porosity dynamics
Billat, P., Vogs, C., Blassiau, C., Brochot, C., Wincent, E., Brion, F., & Beaudouin, R. (2023) · Toxicology in Vitro · doi:10.1016/j.tiv.2023.105588 · Cited by 12 · see citing works
Neurotoxicity and Potential Mechanisms of Exposure to Per- and Polyfluoroalkyl Substances (PFASs)
Song, Y., Ma, Y., Huang, Y., Song, D., Hu, C., Zhang, X., Chen, Y., Zhang, L., & Lu, L. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05573-2 · Cited by 11 · see citing works
“Mice exposed to 0.3 mg/kg/day PFOS accelerated habituation responses when adapted to new environments more rapidly than controls, whereas those exposed to 3 mg/ kg/day PFOS exhibited more intense and disorganized spon-taneous activity [129].”
Influential
Spinal cord injury in zebrafish induced by near-infrared femtosecond laser pulses.
Ellström, I. D., Spulber, S., Hultin, S., Norlin, N., Ceccatelli, S., Hultling, C., & Uhlén, P. (2019) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2018.10.035 · Cited by 9 · see citing works
“Zebrafish locomotor function tests were performed in a behavior experimental setup (DanioVisionTM, Noldus Information Technology, Wageningen, the Netherlands) customized for ambient light control and acoustic stimulation (Spulber et al., 2014).”
Zebrafish models of impulsivity and impulse control disorders
de Abreu, M. S., Giacomini, A. C. V. V., Genário, R., Fontana, B. D., Parker, M. O., Marcon, L., Scolari, N., Bueno, B. W., Demin, K. A., Galstyan, D. S., et al. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.14893 · Cited by 10 · see citing works
Relationship between PFAS and attention-deficit/hyperactivity disorder or autism spectrum disorder: Epidemiological and experimental evidence
Wu, K., Tang, A., Zhang, X., Zhou, S., Wu, N., Tao, J., Chen, Y., Yang, G., Zhou, H., & You, M. (2025) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2025.118519 · Cited by 9 · see citing works
Discovering Novel Bioactivities of Controversial Food Additives by Means of Simple Zebrafish Embryotoxicity (ZET) Assays
Thanh, D. D., Nguyễn, B. N., den Bossche, F. V., Thanh, N. L., & Müller, M. (2022) · Toxics · doi:10.3390/toxics11010008 · Cited by 8 · see citing works
“While hatching stimulation could sometimes be attributed to the embryonic hyperactivity induced by chemicals, e.g., in the case of PFOS [81,82], there are compounds that induced premature hatching and reduced larval locomotion, such as tributyltin [79].”
Background
Temperature-dependent effects of PFOS on risk recognition and fast-start performance in juvenile Spinibarbus sinensis
Xia, J., Ma, Y., Guo, W., Huang, L., & Fu, S. (2015) · Aquatic Biology · doi:10.3354/ab00640 · Cited by 8 · see citing works
Neurobehavioral response in zebrafish exposed to perfluorooctane sulfonate and its substitutes: Underestimated ecological risks
Xie, T., Cui, Y., Ren, Z., Wang, Q., & Chen, M. (2025) · Environmental Pollution · doi:10.1016/j.envpol.2025.126527 · Cited by 7 · see citing works
Mitochondrial and inflammatory dysfunctions underlie perfluorooctane sulfonic acid (PFOS)-induced neurotoxicity in adult zebrafish
de Macedo, G. T., Claro, M. T., Ferreira, S. A., Loreto, J. S., Ajayi, B. O., Prestes, A. D. S., Adedara, I. A., Müller, T. E., dos Santos, M. M., & Barbosa, N. V. (2025) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2025.179972 · Cited by 7 · see citing works
Zebrafish
Rihel, J., & Ghosh, M. (2015) · Springer eBooks · doi:10.1007/978-3-319-05392-9_135 · Cited by 7 · see citing works
Perfluorooctane Sulfonate and Perfluorooctanoic Acid
Viberg, H., & Eriksson, P. O. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804239-7.00043-3 · Cited by 7 · see citing works
Decreased activity in zebrafish larvae exposed to glyphosate-based herbicides during development—potential mediation by glucocorticoid receptor
Spulber, S. D., Reis, L., Alexe, P., & Ceccatelli, S. (2024) · Frontiers in Toxicology · doi:10.3389/ftox.2024.1397477 · Cited by 6 · see citing works
Neurobehavioral Analysis Methods for Adverse Outcome Pathway (AOP) Models and Risk Assessment
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Gutsfeld, S., Wray, C., Schweiger, N., Röhrig, A., Paschke, H., Fu, Q., Kasmanas, J. C., Abdulkadir, N., Kader, S., da Rocha, U. N., et al. (2026) · Environmental Science & Technology · doi:10.1021/acs.est.5c16330 · Cited by 1 · see citing works
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Supercritical Fluid Extraction of Herbal Plants for Safe and Halal Enriched Extracts
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Authors: Spulber, S., Kilian, P., Wan Ibrahim, W. N., Onishchenko, N., Ulhaq, M., Norrgren, L., Negri, S., Di Tuccio, M., & Ceccatelli, S.
Affiliations: Karolinska Institutet (SE)
Swedish University of Agricultural Sciences (SE)
Fondazione Salvatore Maugeri (IT)
Corresponding author: Spulber, Stefan
ORCID: Spulber, Stefan
Onishchenko, Natalia
Negri, Sara
Ceccatelli, Sandra
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2014-04-16
Volume: 9
Issue: 4
Pages: e94227
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0094227
PMC: PMC3989208
OpenAlex: W2054016792
Cited by: 98
References: 71
Citations by year: 2026: 5 · 2025: 10 · 2024: 5 · 2023: 10 · 2022: 16 · 2021: 6 · 2020: 8 · 2019: 13 · 2018: 4 · 2017: 4 · 2016: 7 · 2015: 7 · 2014: 3
FWCI: 5.32
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS ONE (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, other-oa)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Universiti Putra Malaysia Institutional Repository (Universiti Putra Malaysia) (acceptedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Figshare (submittedVersion, cc-by)
Greater South Information System
Funders: Svenska Forskningsrådet Formas
Svenska Sällskapet för Medicinsk Forskning
Karolinska Institutet
Vetenskapsrådet
Topics: Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
Keywords: PFOS, early life exposure, d-amphetamine, dopaminergic system, zebrafish larvae, habituation, startle response, visual motor response, environmental pollutants, ADHD-like behavior
MeSH terms: Animals, Dextroamphetamine, Environmental Exposure, Fluorocarbons, Larva, Swimming, Zebrafish, Akathisia, Drug-Induced, Alkanesulfonic Acids

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PFOS Induces Behavioral Alterations, Including Spontaneous Hyperactivity that Is Corrected by Dexamfetamine in Zebrafish Larvae

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