ArticleEnvironmental health perspectives2007
Nonenzymatic functions of acetylcholinesterase splice variants in the developmental neurotoxicity of organophosphates: chlorpyrifos, chlorpyrifos oxon, and diazinon.
Article in Environmental health perspectives, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Evaluation of developmental toxicity of chlorpyrifos through new approach methodologies: a systematic review.Archives of toxicology · 2025Pooled it
- Bioactivation and detoxification of organophosphorus pesticides in freshwater planarians shares similarities with humans.Archives of toxicology · 2022Article
- Article
- Influence of Gestational Chlorpyrifos Exposure on ASD-like Behaviors in an fmr1-KO Rat Model.Molecular neurobiology · 2022Article
- The ACE genes in Aphelenchoides besseyi isolates and their expression correlation to the fenamiphos treatment.Scientific reports · 2022Article
- Impaired innate and conditioned social behavior in adult C57Bl6/J mice prenatally exposed to chlorpyrifos.Behavioral and brain functions : BBF · 2019Article
- Erythrocyte acetylcholinesterase as biomarker of pesticide exposure: new and forgotten insights.Environmental science and pollution research international · 2018Review
- Effects of Chlorpyrifos or Methyl Parathion on Regional Cholinesterase Activity and Muscarinic Receptor Subtype Binding in Juvenile Rat Brain.Journal of toxicology and pharmacology · 2017Article
- Lactobacillus Casei Decreases Organophosphorus Pesticide Diazinon Cytotoxicity in Human HUVEC Cell Line.Advanced pharmaceutical bulletin · 2016Article
- Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds.Frontiers in neuroscience · 2016Review
- Effects of maternal chlorpyrifos diet on social investigation and brain neuroendocrine markers in the offspring - a mouse study.Environmental health : a global access science source · 2015Article
- Strain dependent effects of conditioned fear in adult C57Bl/6 and Balb/C mice following postnatal exposure to chlorpyrifos: relation to expression of brain acetylcholinesterase mRNA.Frontiers in behavioral neuroscience · 2015Article
- Melatonin protects against diazinon-induced neurobehavioral changes in rats.Neurochemical research · 2013Article
- Acetylcholinesterase as a biomarker in environmental and occupational medicine: new insights and future perspectives.BioMed research international · 2013Review
- The physical environment and child development: an international review.International journal of psychology : Journal international de psychologie · 2013Review
- Does mechanism matter? Unrelated neurotoxicants converge on cell cycle and apoptosis during neurodifferentiation.Neurotoxicology and teratology · 2012Article
- Developmental neurotoxicity of organophosphates targets cell cycle and apoptosis, revealed by transcriptional profiles in vivo and in vitro.Neurotoxicology and teratology · 2012Article
- Developmental exposure to organophosphates triggers transcriptional changes in genes associated with Parkinson's disease in vitro and in vivo.Brain research bulletin · 2011Article
- Repeated developmental exposure of mice to chlorpyrifos oxon is associated with paraoxonase 1 (PON1)-modulated effects on cerebellar gene expression.Toxicological sciences : an official journal of the Society of Toxicology · 2011Article
- Article
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Abstract
backgroundOrganophosphate pesticides affect mammalian brain development through mechanisms separable from the inhibition of acetylcholinesterase (AChE) enzymatic activity and resultant cholinergic hyperstimulation. In the brain, AChE has two catalytically similar splice variants with distinct functions in development and repair. The rare, read-through isoform, AChE-R, is preferentially induced by injury and appears to promote repair and protect against neurodegeneration. Overexpression of the more abundant, synaptic isoform, AChE-S, enhances neurotoxicity.
objectivesWe exposed differentiating PC12 cells, a model for developing neurons, to 30 microM chlorpyrifos (CPF) or diazinon (DZN), or CPF oxon, the active metabolite that irreversibly inhibits AChE enzymatic activity, in order to determine whether they differentially induce the formation of AChE-S as a mechanistic predictor of developmental neurotoxicity. We then administered CPF or DZN to neonatal rats on postnatal days 1-4 using daily doses spanning the threshold for AChE inhibition (0-20%); we then evaluated AChE gene expression in forebrain and brainstem on post-natal day 5.
resultsIn PC12 cells, after 48 hr of exposure, CPF, CPF oxon, and DZN enhanced gene expression for AChE-R by about 20%, whereas CPF and DZN, but not CPF oxon, increased AChE-S expression by 20-40%. Thus, despite the fact that CPF oxon is a much more potent AChE inhibitor, it is the native compound (CPF) that induces expression of the neurotoxic AChE-S isoform. For in vivo exposures, 1 mg/kg CPF had little or no effect, but 0.5 or 2 mg/kg DZN induced both AChE-R and AChE-S, with a greater effect in males.
conclusionsOur results indicate that nonenzymatic functions of AChE variants may participate in and be predictive of the relative developmental neurotoxicity of organophosphates, and that the various organophosphates differ in the degree to which they activate this mechanism.
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