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

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.

PFOS, PFNA, and PFOA sub-lethal exposure to embryonic zebrafish have different toxicity profiles in terms of morphometrics, behavior and gene expression

“…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). However, this does not correlate with the difference in total body size (PFOA significantly smaller, PFNA significantly larger, PFOS no change).…”

Behavioral, morphometric, and gene expression effects in adult zebrafish (Danio rerio) embryonically exposed to PFOA, PFOS, and PFNA

“…Additional behavior effects included changes in swimming velocity (PFNA, PFOS) and thigmotaxis behaviors (PFNA, PFOS). 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). Analyzing similar behavior endpoints in adult zebrafish will determine if the growth and behavior affects seen in larval zebrafish persist through adulthood as well as better understand the long term effects of PFAS exposure in our teleost model system.…”

Temperature-dependent effects of PFOS on risk recognition and fast-start performance in juvenile Spinibarbus sinensis

“…As reported by Spulber et al (2014), zebrafish larvae exposed to 1 mg l −1 PFOS displayed a disorganized pattern of spontaneous activity and persistent hyperactivity. In the current study, we clearly demonstrated that 2 mg l −1 PFOS exposure at 28°C resulted in a reduced antipredator response by the fish, manifested as a higher frequency of use of the risky area, an increased percentage of time that the fish spent in the risky area, and a strong decrease in the average distance to the predator.…”