Neurotoxic Effects and Biomarkers of Lead Exposure: A Review Original paper

What was studied?

The review article delves into the neurotoxic effects of lead exposure, focusing on how lead disrupts brain function at a molecular level. Lead, a well-known environmental toxin, is capable of crossing the blood-brain barrier and accumulating in the brain, where it causes significant damage. The article explores the mechanisms by which lead affects neuronal function, particularly through ion mimicry. Lead substitutes for calcium and other essential divalent cations in the brain, disrupting critical signaling pathways, neurotransmitter release, and synaptic function. The review also highlights lead’s effects on mitochondrial function, where it interferes with cellular energy production and increases oxidative stress, leading to neurodegeneration. Additionally, it discusses the role of lead in neuroinflammation, which exacerbates neuronal damage, and provides insights into biomarkers that can help assess lead exposure and its neurotoxic effects, such as blood lead levels (BPb), bone lead (BnPb), and δ-aminolevulinic acid dehydratase (δ-ALAD) activity.

Who was studied?

The review synthesizes findings from a variety of studies, including animal models and human clinical studies, which examine the neurotoxic effects of lead exposure across different populations. In experimental animal studies, particularly with rodents, lead was administered via different routes such as oral ingestion, injection, or water to simulate human exposure. These studies focus on understanding how lead exposure disrupts cognitive function, behavior, and brain development. In human studies, the review examines the effects of lead exposure in both children and adults, particularly those who have been exposed in occupational or high-risk environmental settings. These clinical studies provide important data on how lead exposure, even at low levels, can result in cognitive impairments, behavioral changes, and an increased risk of neurodegenerative diseases. The review also emphasizes the vulnerability of children, who are especially sensitive to the neurotoxic effects of lead, and discusses the long-term impacts of early-life exposure.

Most important findings

The most significant findings of the review underscore the molecular pathways through which lead disrupts brain function. Lead’s ability to mimic calcium ions is a central mechanism, allowing it to enter neurons and interfere with calcium-dependent processes such as neurotransmitter release, synaptic plasticity, and overall neuronal signaling. This interference in cellular processes is key to understanding the cognitive deficits and behavioral changes associated with lead exposure. Additionally, the review highlights how lead induces mitochondrial dysfunction, which reduces ATP production and increases oxidative stress. This oxidative stress damages neurons and contributes to the development of neurodegenerative diseases. Another critical finding is the neuroinflammatory response triggered by lead exposure, which further exacerbates neuronal damage by activating glial cells and releasing inflammatory cytokines.

These processes collectively lead to the long-term cognitive and behavioral impairments seen in individuals with lead exposure, including memory problems, attention deficits, and hyperactivity. The review also discusses biomarkers of lead exposure, such as blood lead levels (BPb) and bone lead (BnPb), which serve as indicators of both recent and long-term exposure. These biomarkers help clinicians assess the neurotoxic burden of lead in individuals and understand its impact on brain function.

Key implications

The findings of this review have significant clinical and public health implications. Clinicians should be aware that low-level chronic lead exposure can have long-term neurotoxic effects, particularly on cognitive function and behavior. Early identification of lead exposure through biomarkers, such as BPb and BnPb, is critical for managing and mitigating the effects of lead toxicity. Interventions, including chelation therapy, antioxidant treatments, and anti-inflammatory strategies, may help alleviate the damage caused by lead exposure, particularly in children who are most vulnerable to its effects. Public health strategies should focus on reducing environmental and occupational lead exposure, especially in communities with high levels of contamination, to prevent the neurotoxic effects of lead. Moreover, for microbiome researchers, the review suggests that lead exposure could influence the gut-brain axis, which may alter microbial signatures related to neurodevelopmental and neurodegenerative diseases.