Abstract
Few studies have assessed the effects of developmental methylmercury (MeHg) exposure on learning and memory at different ages. The possibility of the amelioration or worsening of the effects has not been sufficiently investigated. This study aimed to assess whether low-dose MeHg exposure in utero and during suckling induces differential disturbances in learning and memory of periadolescent and young adult rats. Four experimental groups of pregnant Sprague-Dawley rats were orally exposed to MeHg or vehicle from gestational day 5 to weaning: (1) control (vehicle), (2) 250 μg/kg/day MeHg, (3) 500 μg/kg/day MeHg, and (4) vehicle, and treated on the test day with MK-801 (0.15 mg/kg i.p.), an antagonist of the N-methyl D-aspartate receptor. The effects were evaluated in male offspring through the open field test, object recognition test, Morris water maze, and conditioned taste aversion. For each test and stage assessed, different groups of animals were used. MeHg exposure, in a dose-dependent manner, disrupted exploratory behaviour, recognition memory, spatial learning, and acquisition of aversive memories in periadolescent rats, but alterations were not observed in littermates tested in young adulthood. These results suggest that developmental low-dose exposure to MeHg induces age-dependent detrimental effects. The relevance of decreasing exposure to MeHg in humans remains to be determined.
Highlights
Developmental exposure to environmental pollutants has been associated with the onset of cognitive disturbances, due to the sensitivity of the immature central nervous system (CNS) to external insults
These findings could be explained by several factors such as the following: (a) the MeHg dose received by the pups was not sufficient to cause longlasting adverse effects and compensatory systems could act to overcome the detrimental effects observed at postnatal day- (PND-)40; (b) the effects observed at PND-40 may be due to alterations in neurotransmission or synaptogenesis; (c) the younger CNS is more vulnerable to detrimental effects of MeHg
The data from PND-40 are consistent with the literature [39, 40], and the age-dependent nature of the effect suggests a subtle alteration in the cerebellum, which is not strong enough to remain after the exposure is discontinued, when compensatory mechanisms could counteract the effect
Summary
Developmental exposure to environmental pollutants has been associated with the onset of cognitive disturbances, due to the sensitivity of the immature central nervous system (CNS) to external insults. Data from experimental studies suggests that neonatal exposure to low-doses of MeHg is associated with visual, memory, and social alterations in nonhuman primates [15,16,17], memory deficits, and depressive-like behaviour in mice [18] and at higher doses (>3,000 μg/kg/day) severe motor dysfunction and cognitive deficits [19]. Rats, due to their toxicokinetics, must consume 10-fold higher doses of MeHg than humans, nonhuman primates, and mice to achieve similar brain Hg levels and present neurotoxic effects [20, 21]. Experimental evidence from pregnant rats exposed to daily doses of 500 μg/kg of MeHg showed that MeHg levels in BioMed Research International the brain of pups reached concentrations in the range of MeHg levels found in the brains of infants from populations exposed through fish consumption [20, 22]
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