ArticleToxicology and applied pharmacology2008
Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the morphogenic activity of acetylcholinesterase.
Article in Toxicology and applied pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- Evaluation of developmental toxicity of chlorpyrifos through new approach methodologies: a systematic review.Archives of toxicology · 2025Pooled it
- Fucoxanthinol Mitigates the Cytotoxic Effect of Chlorpyrifos and MPTP on the Dopaminergic Differentiation of SH-SY5Y Human Neuroblastoma Cells.Journal of molecular neuroscience : MN · 2025Article
- Assessing the Risks of Pesticide Exposure: Implications for Endocrine Disruption and Male Fertility.International journal of molecular sciences · 2024Review
- Prediction ofFrontiers in pharmacology · 2023Article
- Bioactivation and detoxification of organophosphorus pesticides in freshwater planarians shares similarities with humans.Archives of toxicology · 2022Article
- Modulation of CREB and its associated upstream signaling pathways in pesticide-induced neurotoxicity.Molecular and cellular biochemistry · 2022Review
- Prenatal exposure to organophosphate pesticides and risk-taking behaviors in early adulthood.Environmental health : a global access science source · 2022Article
- Differences in neurotoxic outcomes of organophosphorus pesticides revealedFrontiers in toxicology · 2022Article
- Gestational Exposure to Organophosphate Pesticides and Longitudinally Assessed Behaviors Related to Attention-Deficit/Hyperactivity Disorder and Executive Function.American journal of epidemiology · 2021Article
- Gene-Environment Interactions in Developmental Neurotoxicity: a Case Study of Synergy between Chlorpyrifos and CHD8 Knockout in Human BrainSpheres.Environmental health perspectives · 2021Article
- Associations between pesticide mixtures applied near home during pregnancy and early childhood with adolescent behavioral and emotional problems in the CHAMACOS study.Environmental epidemiology (Philadelphia, Pa.) · 2021Article
- Gestational exposures to organophosphorus insecticides: From acute poisoning to developmental neurotoxicity.Neuropharmacology · 2020Review
- Neurite outgrowth inhibitory levels of organophosphates induce tissue transglutaminase activity in differentiating N2a cells: evidence for covalent adduct formation.Archives of toxicology · 2020Article
- Review
- Increased severity of fragile X spectrum disorders in the agricultural community of Ricaurte, Colombia.International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience · 2019Article
- Mechanisms of organophosphorus pesticide toxicity in the context of airway hyperreactivity and asthma.American journal of physiology. Lung cellular and molecular physiology · 2018Review
- Article
- Neurotoxicity in acute and repeated organophosphate exposure.Toxicology · 2018Review
- Cholinesterases and the fine line between poison and remedy.Biochemical pharmacology · 2018Review
- A Novel Method for the Development of Environmental Public Health Indicators and Benchmark Dose Estimation Using a Health-Based End Point for Chlorpyrifos.Environmental health perspectives · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrations that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE -/-) versus wild type (AChE +/+) mice indicated that while these OPs inhibited axonal growth in AChE+/+ DRG neurons, they had no effect on axonal growth in AChE -/- DRG neurons. However, transfection of AChE -/- DRG neurons with cDNA encoding full-length AChE restored the wild type response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs.
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