Effects of PFOS, F-53B and OBS on locomotor behaviour, the dopaminergic system and mitochondrial function in developing zebrafish (Danio rerio). (1st June 2023) - Kalyn, Michael
Abstract: Perfluorooctanesulfonic acid (PFOS) has widely been reported to persist in the environment and to elicit neurotoxicological effects in wildlife and humans. Following the restriction of PFOS use, 6:2 chlorinated polyfluorinated ether sulfonate (F-53B) and sodium p-perfluorous nonenoxybenzene sulfonate (OBS) have emerged as novel PFOS alternatives and have been detected in the environment. However, knowledge on the toxicological effects of these alternatives remains scarce. Using developing transgenic Tg( dat:eGFP ) zebrafish, we evaluated the consequences of exposure to 0, 0.1 and 1 mg/l PFOS, F-53B and OBS on the dopaminergic system, locomotor behaviour and mitochondrial function. All compounds generally reduced locomotor activity under light conditions irrespective of exposure concentration. Exposure to OBS (at all concentrations), as well as PFOS and F-53B (at 1 mg/l), significantly reduced subpallial dopaminergic neuron abundance. PFOS also significantly reduced dat and pink1 expression irrespective of exposure concentration, while F-53B and OBS tended to reduce mitochondrial pink1 and fis1 expression across concentrations without reaching statistical significance. Mitochondrial function, in the form of reduced oxygen consumption rate and marginally inhibited ATP-linked oxygen consumption rate, was affected only in response to 1 mg/l PFOS. Together, PFOS and the emerging contaminants F-53B and OBS inhibit locomotion at similar concentrations, a finding correlated with decreased dopaminergic neuron numbers in the subpallium and decreased expression of pink1 . These findings are relevant to wildlife and human health, as they suggest that PFOS as well as replacement compounds affect locomotion likely in part by negatively impacting the dopamine system. Graphical abstract: Image 1 Highlights: Exposure to the PFOS, F–53 B and OBS results in hypo-locomotion. The hypo-locomotion is mediated by reductions in larger distances travelled. Exposure to the PFOS, F–53 B and OBS reduces subpallial DA neuron numbers. PFOS specifically reduces transcript abundance of dat and pink1 . PFOS and OBS reduce OCR levels and disrupt mitochondrial bioenergetic functions.