New findings on mercury neurotoxicity in fish unveiled by oxidative stress profiles in the brain and neurotransmission status upon exposure to inorganic and organic forms

Methylmercury (MeHg) is widely known for its neurotoxicity in humans and other mammals, while this is less reported in fish. Additionally, the ability of inorganic Hg (iHg) to exert toxicity in fish brain remains elusive,... [ view full abstract ]

Methylmercury (MeHg) is widely known for its neurotoxicity in humans and other mammals, while this is less reported in fish. Additionally, the ability of inorganic Hg (iHg) to exert toxicity in fish brain remains elusive, which is puzzling considering that Hg is present in the water mainly as inorganic forms. The current research is a step forward in the understanding of both MeHg and iHg neurotoxicity in fish by covering their temporal accumulation in the brain, together with an evaluation of their toxicity mechanisms. White seabream juveniles (Diplodus sargus) were exposed to waterborne Hg²⁺ (2 µg L^-1) and dietary MeHg (8.7 µg g^-1), corresponding to a similar daily intake rate (around 30 µg Hg/day/fish), thereby allowing a toxicokinetics comparison of both forms. A control group was kept throughout both experiments that comprised 4 exposure (days 1, 3, 7 and 14) and 2 post-exposure (days 14 and 28) periods. At each time-point, brain was collected for determination of total Hg levels, antioxidants, cellular damage indicators and acetylcholinesterase (AChE) activity. MeHg and iHg followed an identical time-variation pattern in the brain with both forms increasing significantly after 3 days of exposure. Despite that, MeHg exposure was on the basis of higher Hg levels (2- to 6-fold) when compared to iHg exposure, pointing out the highly efficient transport of MeHg to the fish brain. Interestingly, iHg was not significantly eliminated from the brain during 28 days of depuration, while Hg levels decreased at the end of the post-exposure period for MeHg. Fascinatedly, MeHg activated the antioxidant defences in the brain (mainly SOD, CAT, GPx and GST), while iHg hampered the glutathione system as demonstrated by the significant inhibition of GPx. Accordingly, the damage of lipids and proteins was more efficiently prevented by the antioxidant defence system upon MeHg exposure than to iHg. In general, AChE did not change in the brain of MeHg-exposed fish, while a decrease was found with iHg accumulation, unveiling an eventual compromise of the synaptic transmission. Despite the higher accumulation of Hg upon MeHg exposure, fish brain displayed higher susceptibility to iHg as depicted by the occurrence of oxidative damage, less responsiveness of the antioxidant system and anticholinergic action. Therefore, the neurotoxic potential of iHg in fish should not be disregarded and thus, its lower exposure risk (in comparison with MeHg), as claimed in the literature, needs to be rethought in the planning and interpretation of environmental health assessments. Since Hg has a high potential to be accumulated in the food chain, effects of Hg on ecosystems functioning, human health and sustainable development need to be considered at the light of the current findings.

Keywords: Inorganic mercury; Methylmercury; Neurotoxicity; Oxidative stress; Brain; Fish