Cognitive outcomes caused by low-level lead, cadmium, and mercury mixture exposure at distinct phases of brain development

Contaminated water and food are the main sources of lead, cadmium, and mercury in the human body. Long-term and low-level ingestion of these toxic heavy metals may affect brain development and cognition. Howev-er, the neurotoxic effects of exposure to lead, cadmium, and mercury mixture (Pb + Cd + Hg) at different stages of brain development are rarely elucidated. In this study, different doses of low-level Pb + Cd + Hg were administered to Sprague-Dawley rats via drinking water during the critical stage of brain development, late stage, and after maturation, respectively. Our findings showed that Pb + Cd + Hg exposure decreased the density of memory-and learning-related dendritic spines in the hippocampus during the critical period of brain devel-opment, resulting in hippocampus-dependent spatial memory deficits. Only the density of learning-related dendritic spines was reduced during the late phase of brain development and a higher-dose of Pb + Cd + Hg exposure was required, which led to hippocampus-independent spatial memory abnormalities. Exposure to Pb + Cd + Hg after brain maturation revealed no significant change in dendritic spines or cognitive function. Further molecular analysis indicated that morphological and functional changes caused by Pb + Cd + Hg exposure during the critical phase were associated with PSD95 and GluA1 dysregulation. Collectively, the effects of Pb + Cd + Hg on cognition varied depending on the brain development stages.

Automated summary

Contaminated water and food are the main sources of lead, cadmium, and mercury in the human body, and their long-term and low-level ingestion can affect brain development and cognition. This study investigated the neurotoxic effects of exposure to a mixture of lead, cadmium, and mercury at different stages of brain development. The results showed that exposure during the critical period of brain development resulted in spatial memory deficits, while exposure during the late phase led to spatial memory abnormalities. However, exposure after brain maturation had no significant effects on cognitive function.