Insights into cognitive deficits caused by low-dose toxic heavy metal mixtures and their remediation through a postnatal enriched environment in rats

Abstract The heavy metals, namely lead (Pb), cadmium (Cd), and mercury (Hg), have been studied extensively in various independent studies. It has been seen that these metals are usually detected simultaneously in the human blood at low levels. However, it is unknown whether exposure to these heavy metal mixtures (MM) can induce neurological damages at these low levels. Therefore, we investigated the influence of the Pb, Cd, and Hg mixture on the nervous system in rats at exposure doses equivalent to those normally found in the human blood. After pregnant rats being exposed to MM via drinking water throughout the gestation and lactation, their offspring were followed-up till adulthood. MM caused cognitive deficits and impairments in a dose-dependent manner. Furthermore, MM disrupted dendritic spines, the structural basis of learning and memory, and induced changes in spine-related pathways. Meanwhile, we explored an early and safe way to remedy these impairments through a postnatal enriched environment. The enriched environment ameliorated MM-impaired cognitive function, synaptic plasticity, and spine-related pathways. This study demonstrated that low-dose co-exposure to Pb, Cd, and Hg can cause cognitive and synaptic plasticity deficits and timely intervention through the enriched environment has a certain corrective effect.