Effects of perinatal exposure to n-3 polyunsaturated fatty acids and methylmercury on cerebellar and behavioral parameters in mice

Abstract

Fish and shellfish, which represent important sources of nutrients (i.e., n-3 fatty acids), can contain significant amounts of methylmercury (MeHg), a neurotoxic compound. We investigated the potential neuroprotective effects of perinatal treatment with dietary n-3 fatty acids against MeHg-induced neurotoxicity. Pregnant mice were divided in 4 groups: (i) Control; (ii) MeHg; (iii) n-3 enriched diet and (iv) n-3 enriched diet + MeHg. The treatments were performed from gestational day 1 to postnatal day 21. Twenty-four hours after treatments, motor-related behavioral tests, as well as the analyses of cerebellar biochemical, histological and immunohistochemical parameters related to neuronal and glial homeostasis, were performed. Maternal exposure to MeHg induced motor coordination impairment and cerebellar MeHg accumulation in the offspring and n-3 fatty acids treatment did not prevent these effects. The immunocontent of proteins related to synaptic homeostasis, glial fibrillary acidic protein immunostaining and morphology were not significantly altered in the pups perinatally exposed to MeHg and/or n-3 diet. The results indicate that perinatal exposure to MeHg causes motor coordination impairment even with no evident changes on the evaluated cerebellar biochemical and histological parameters. The performed exposure protocol was unable to show beneficial effects of n-3 fatty acids supplementation against MeHg-induced motor coordination.

Methylmercury exposure during prenatal and postnatal neurodevelopment promotes oxidative stress associated with motor and cognitive damages in rats: an environmental-experimental toxicology study

“…Interestingly, our model used a low dose for long periods of exposure, and manages to trigger outcomes similar to those found in populations exposed to MeHg, for example: evidence of motor deficits and neuronal impairment was found [22] associated with motor cortex of rats, in addition to up-regulation of Apolipoprotein E in the hippocampus [18] , which has been reported as an important biomarker of mercury exposure in riverine populations [55] associated with cognitive damage. Based on the reports in the literature that show perinatal and postnatal exposure to methylmercury and its consequences in the cerebellum and hippocampus, we know that the deleterious effects are caused by different doses of intoxication to MeHg and different protocols of exposure to the metal (Ghizoni et al [59] ; Cheng et al [60] ). Thus, the novelty proposed in this study is the exposure during the gestational and lactational period to a low dose (40 μg/kg/day) for a long period, in a model that allows animals to be exposed to MeHg in a way that simulates human exposure in the environment, representing the chronic exposure to MeHg of environmentally vulnerable populations with high mercury levels, such as those found in the Amazon ( [56] ; Berzas Nevado et al [61] ).…”