Neurodevelopmental Consequences Induced by Early-Life Lead Exposure Through Disruption of Neurotransmitter Pathways and Molecular Mechanisms: A Systematic Review.

Abstract

Lead is a toxic heavy metal with significant health risks, as maternal lead exposure during pregnancy disrupts fetal neural development through placental transfer, leading to persistent neurological, developmental, and long-term health consequences in the progeny. Lead exposure typically affects the central nervous system, which is especially harmful during fetal development and early infancy. This review emphasizes the impact of early developmental exposure leading to disruption of neurotransmitter mechanisms. Mechanistically, lead disrupts neurodevelopment through various pathways, including alterations in myelin proteins, synaptic function, and neuroinflammatory responses, by interfering with the regulatory action of calcium, as lead mimics and replaces calcium. Alterations caused by lead, particularly in the dopaminergic, cholinergic, glutamatergic, and GABAergic pathways, increase the risk of neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and cognitive disabilities in children. Lead is known to induce cellular, molecular, and epigenetic changes that impair neuronal connectivity, synaptic plasticity, and network functionality, ultimately leading to the disruption of neurodevelopmental pathways. The cumulative evidence highlights various aspects of lead neurotoxicity and emphasizes its role in the etiology of neurodevelopmental impairments. Understanding these pathways is critical for early intervention strategies to mitigate the long-term cognitive and behavioral consequences of lead exposure during sensitive developmental periods.