Lead (Pb) Exposure, Neurotransmitter Dysregulation, and Neurodevelopmental Toxicity in Children: A PRISMA-Guided Systematic Review.

Authors

Iskandar, Rizmi Yunita, Didik Dwi Sanyoto, Isna Syauqiah, Eko Suhartono

Published in

Journal of applied toxicology : JAT. Aug 07, 2026. Epub Aug 07, 2026.

Abstract

Lead (Pb) is a persistent environmental toxicant and a major risk factor for impaired neurodevelopment in children. Although Pb exposure has long been associated with cognitive, behavioral, and developmental abnormalities, the underlying mechanistic evidence remains fragmented. This systematic review aimed to synthesize current evidence on Pb-induced disruption of neurotransmitter systems and associated neurodevelopmental toxicity. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Literature searches were conducted in PubMed and Scopus for studies published between January 2015 and December 2025. Studies were eligible if they examined Pb exposure in relation to neurotransmitter dysregulation, neurotoxicity, or neurodevelopmental outcomes in human, animal, or in vitro models. Of the 73 records identified, 41 studies met the inclusion criteria, including 32 animal studies, 6 human observational studies, and 3 in vitro studies. Across the included studies, Pb exposure was consistently associated with disruption of dopaminergic, serotonergic, glutamatergic, and GABAergic pathways, together with altered expression of neurotransmitter-related genes, impaired maturation of inhibitory circuits, and behavioral abnormalities. In vitro studies further demonstrated calcium (Ca)-dependent synaptic dysfunction, oxidative stress, endoplasmic reticulum stress, and impaired neurite development. Human studies supported these findings by linking blood Pb levels with neurobehavioral deficits and altered neurotransmitter-related biomarkers. Overall, the evidence indicates that Pb exerts developmental neurotoxicity through converging mechanisms involving Ca dysregulation, synaptic impairment, oxidative stress, and neurotransmitter imbalance. These findings provide an integrated mechanistic framework for understanding how environmental Pb exposure contributes to neurodevelopmental dysfunction in children.

PMID:
42567841
Bibliographic data and abstract were imported from PubMed on 08 Aug 2026.

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