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Lead (Pb) Exposure, Neurotransmitter Dysregulation, and Neurodevelopmental Toxicity in Children: A PRISMA-Guided
Iskandar1,2,3, Rizmi Yunita4, Didik Dwi Sanyoto5
1Environmental Science, Universitas Lambung Mangkurat, Banjarmasin, South Kalimantan, Indonesia.
Insights
Lead exposure harms children's neurodevelopment by disrupting key brain chemical systems. This review synthesizes evidence showing lead (Pb) impacts neurotransmitters, leading to cognitive and behavioral issues through various toxic mechanisms.
Area of Science:
- Environmental Health
- Neuroscience
- Toxicology
Background:
- Lead (Pb) is a pervasive environmental toxicant.
- Pb exposure is a significant risk factor for neurodevelopmental deficits in children.
- Existing mechanistic evidence linking Pb to neurotoxicity is fragmented.
Purpose of the Study:
- To systematically review and synthesize evidence on lead-induced disruption of neurotransmitter systems.
- To elucidate the mechanisms of lead's neurodevelopmental toxicity.
- To provide an integrated framework for understanding Pb neurotoxicity.
Main Methods:
- Systematic literature review following PRISMA 2020 guidelines.
- Searched PubMed and Scopus for studies (2015-2025) on Pb exposure and neurotransmitter/neurodevelopmental outcomes.
- Included human, animal, and in vitro studies.
Main Results:
- Pb exposure consistently disrupts dopaminergic, serotonergic, glutamatergic, and GABAergic pathways.
- Observed altered neurotransmitter gene expression, impaired inhibitory circuit maturation, and behavioral abnormalities.
- In vitro and human studies confirmed Pb-induced synaptic dysfunction, oxidative stress, and neurobehavioral deficits.
Conclusions:
- Lead exerts developmental neurotoxicity via integrated mechanisms including calcium dysregulation, synaptic impairment, oxidative stress, and neurotransmitter imbalance.
- This provides a mechanistic framework for Pb's contribution to neurodevelopmental dysfunction.
- Highlights the critical need for reducing environmental lead exposure in children.
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.
