Cognitive Impairment Induced by Lead Exposure during Lifespan: Mechanisms of Lead Neurotoxicity

Abstract

Lead (Pb) is considered a strong environmental toxin with human health repercussions. Due to its widespread use and the number of people potentially exposed to different sources of this heavy metal, Pb intoxication is recognized as a public health problem in many countries. Exposure to Pb can occur through ingestion, inhalation, dermal, and transplacental routes. The magnitude of its effects depends on several toxicity conditions: lead speciation, doses, time, and age of exposure, among others. It has been demonstrated that Pb exposure induces stronger effects during early life. The central nervous system is especially vulnerable to Pb toxicity; Pb exposure is linked to cognitive impairment, executive function alterations, abnormal social behavior, and fine motor control perturbations. This review aims to provide a general view of the cognitive consequences associated with Pb exposure during early life as well as during adulthood. Additionally, it describes the neurotoxic mechanisms associated with cognitive impairment induced by Pb, which include neurochemical, molecular, and morphological changes that jointly could have a synergic effect on the cognitive performance.

Keywords: cognition; heavy metals; lead; neurotoxicity.

Figure 1

Cognitive and behavioral changes induced by Pb exposure in humans and associated morphologic, cellular, and molecular alterations of Pb toxicity.

Figure 2

Mechanisms involved in Pb toxicity in the CNS. Pb can enter the CNS through DMT1 and calcium transporters. In the presynaptic neuron, Pb binds with greater affinity to voltage-gated calcium channels and decreases transportation of calcium ions. Through these channels, Pb can cross inside the cell. Once inside, Pb interacts through Ca²⁺ binding sites, with several neuronal components involved in vesicular mobilization and docking, affecting the vesicular mobilization and the neurotransmitter release, thus decreasing the activation of postsynaptic receptors. Pb can form Pb–NMDA complexes altering the intracellular levels of Ca²⁺ in the postsynaptic neuron. The kynurenic acid produced in the astrocytes and rise by Pb contributes to LTP dysfunction. Finally, Pb alters the redox environment, promoting an oxidant environment and cell death.