PFOS induces behavioral alterations, including spontaneous hyperactivity that is corrected by dexamfetamine in zebrafish larvae.

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

doi:10.1371/journal.pone.0094227

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.

Highlights

Perfluorinated compounds (PFCs) are a family of chemical compounds that are very stable in the environment due to the carbon-fluorine bonds
We found a significant decrease in the number of spontaneous bouts of activity associated with an increase in the intensity of activity within the bout occurred only in the mice exposed to 3 mg/kg/day, but not in the 0.3 mg/kg/day Perfluorooctane sulfonate (PFOS)-exposed mice (Fig. 1 E, F)
We found that 1 mM dexamfetamine induced hyperactivity in controls and in larvae exposed to 0.1 mg/ L PFOS by increasing the frequency of spontaneous activity bouts, but did not alter the distance moved within a bout (Fig 4 A)

Summary

Introduction

Perfluorinated compounds (PFCs) are a family of chemical compounds that are very stable in the environment due to the carbon-fluorine bonds (reviewed in [1]). Perfluorooctane sulfonate (PFOS) is a member of the PFCs family that has been used in a wide range of industrial and commercial applications for the past 50 years and is the most commonly found in a large number of biomonitoring samples from the human general population and wildlife [2,3,4]. Prenatal exposure to PFOS has not been found to be associated to neurodevelopmental deficits in children up to the age of 7 [8,13,14]. Two cross-sectional studies report an association between blood levels of PFOS and impulsivity [15] and the prevalence of attention deficit hyperactive disorder (ADHD) [16] in children aged 9–11 and 12–15, respectively

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