Developmental exposure to Pb and Mn in mice: Longitudinal studies

Developmental exposure to metals may have serious consequences for mental health1,2. Longitudinal in vivo studies can improve our ability to identify mechanisms of metal neurotoxicity and consistency of long term effects. In our first study, we developmentally exposed CD1 outbred mice to Pb, in the second one to a mixture of Pb and Mn. We mimicked the real-life exposure scenario with low, human-related levels of the two metals administered in drinking water to female mice throughout pre-conception, gestation and lactation periods. Behavioural tests were subsequently conducted in the offspring (to evaluate metal effects on neonatal, juvenile and adult behavioural profiles). Metal levels were monitored in blood, brain and bone at different ages. The first study revealed the effect of Pb on selected neonatal responses (reduced locomotor activity in the nest area during homing test on PND 11 and spatial learning and memory performances at adulthood. These behavioural alterations were observed in animals with blood lead levels (BBLs) below 5 µg/dL, the identified blood Pb reference value for children by the Center for Disease Control and Prevention (CDC)3, thus confirming that that there is no safe level for Pb. Moreover, Pb monitoring in different tissue showed that brain Pb levels remain significantly higher than controls at later ages, when BLLs did not longer differ. Interestingly, adult Pb-exposed males appeared more vulnerable than females to detrimental Pb effects on spatial learning and memory, as previously reported4; brain Pb levels in males did not differ from females, suggesting a different Pb neurodevelopmental effect rather than higher accumulation in male brains. In the second experiment, whereas most Pb effects of the previous study were confirmed, co-exposure of Pb and Mn did not show synergistic effect of the two metals; Mn-exposed males appeared selectively impaired in reactivity to social/olfactory cues, a result that certainly needs further investigation. As a whole, we found behavioural effects of developmental metal exposures, suggesting that Pb and Mn interfered with maturation of cognitive and social competencies.