ArticleTranslational psychiatry2015
Early-life lead exposure recapitulates the selective loss of parvalbumin-positive GABAergic interneurons and subcortical dopamine system hyperactivity present in schizophrenia.
Article in Translational psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 58 citations in OpenAlex.
- Article
- Glutamate-Mediated Neural Alterations in Lead Exposure: Mechanisms, Pathways, and Phenotypes.Toxics · 2025Review
- Chronic PbbioRxiv : the preprint server for biology · 2025Article
- Article
- Laminar Distribution of Cannabinoid Receptor 1 in the Prefrontal Cortex of Nonhuman Primates.Molecular neurobiology · 2024Article
- Early-Life Lead Exposure: Risks and Neurotoxic Consequences.Current medicinal chemistry · 2024Review
- The Co-Expression Pattern of Calcium-Binding Proteins with γ-Aminobutyric Acid and Glutamate Transporters in the Amygdala of the Guinea Pig: Evidence for Glutamatergic Subpopulations.International journal of molecular sciences · 2023Article
- Article
- Cortical interneurons in schizophrenia - cause or effect?Croatian medical journal · 2023Review
- Chronic N-Acetylcysteine Treatment Prevents Amphetamine-Induced Hyperactivity in HeterozygousInternational journal of molecular sciences · 2022Article
- Chronic early-life lead exposure sensitizes adolescent rats to cocaine: Role of the dopaminergic system.Frontiers in molecular neuroscience · 2022Article
- Combined Exposure to Metals in Drinking Water Alters the Dopamine System in Mouse Striatum.International journal of environmental research and public health · 2021Article
- Early-life lead exposure and neurodevelopmental disorders.Current opinion in toxicology · 2021Article
- Chronic developmental lead exposure increases μ-opiate receptor levels in the adolescent rat brain.Neurotoxicology · 2021Article
- Interneuron Heterotopia in the Lis1 Mutant Mouse Cortex Underlies a Structural and Functional Schizophrenia-Like Phenotype.Frontiers in cell and developmental biology · 2021Article
- A Selective Review of the Excitatory-Inhibitory Imbalance in Schizophrenia: Underlying Biology, Genetics, Microcircuits, and Symptoms.Frontiers in cell and developmental biology · 2021Review
- (Ascorb)ing Pb Neurotoxicity in the Developing Brain.Antioxidants (Basel, Switzerland) · 2020Review
- Beyond the looking glass: recent advances in understanding the impact of environmental exposures on neuropsychiatric disease.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Review
- Article
- Metal Toxicity Links to Alzheimer's Disease and Neuroinflammation.Journal of molecular biology · 2019Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Environmental factors have been associated with psychiatric disorders and recent epidemiological studies suggest an association between prenatal lead (Pb(2+)) exposure and schizophrenia (SZ). Pb(2+) is a potent antagonist of the N-methyl-D-aspartate receptor (NMDAR) and converging evidence indicates that NMDAR hypofunction has a key role in the pathophysiology of SZ. The glutamatergic hypothesis of SZ posits that NMDAR hypofunction results in the loss of parvalbumin (PV)-positive GABAergic interneurons (PVGI) in the brain. Loss of PVGI inhibitory control to pyramidal cells alters the excitatory drive to midbrain dopamine neurons increasing subcortical dopaminergic activity. We hypothesized that if Pb(2+) exposure in early life is an environmental risk factor for SZ, it should recapitulate the loss of PVGI and reproduce subcortical dopaminergic hyperactivity. We report that on postnatal day 50 (PN50), adolescence rats chronically exposed to Pb(2+) from gestation through adolescence exhibit loss of PVGI in SZ-relevant brain regions. PV and glutamic acid decarboxylase 67 kDa (GAD67) protein were significantly decreased in Pb(2+) exposed rats with no apparent change in calretinin or calbindin protein levels suggesting a selective effect on the PV phenotype of GABAergic interneurons. We also show that Pb(2+) animals exhibit a heightened locomotor response to cocaine and express significantly higher levels of dopamine metabolites and D2-dopamine receptors relative to controls indicative of subcortical dopaminergic hyperactivity. Our results show that developmental Pb(2+) exposure reproduces specific neuropathology and functional dopamine system changes present in SZ. We propose that exposure to environmental toxins that produce NMDAR hypofunction during critical periods of brain development may contribute significantly to the etiology of mental disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.