ArticleToxicological sciences : an official journal of the Society of Toxicology2012
Delayed reduction of hippocampal synaptic transmission and spines following exposure to repeated subclinical doses of organophosphorus pesticide in adult mice.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 52 citations in OpenAlex.
- Oxime-functionalized anti-insecticide fabric reduces insecticide exposure through dermal and nasal routes, and prevents insecticide-induced neuromuscular-dysfunction and mortality.Nature communications · 2024Article
- Ketamine Produces Antidepressant Effects by Inhibiting Histone Deacetylases and Upregulating Hippocampal Brain-Derived Neurotrophic Factor Levels in a Diisopropyl Fluorophosphate-Based Rat Model of Gulf War Illness.The Journal of pharmacology and experimental therapeutics · 2024Article
- The susceptibility of humans to neurodegenerative and neurodevelopmental toxicities caused by organophosphorus pesticides.Archives of toxicology · 2023Review
- Pyridostigmine bromide, chlorpyrifos, and DEET combined Gulf War exposure insult depresses mitochondrial function in neuroblastoma cells.Journal of biochemical and molecular toxicology · 2021Article
- Rabbit Antidiethoxyphosphotyrosine Antibody, Made by Single B Cell Cloning, Detects Chlorpyrifos Oxon-Modified Proteins in Cultured Cells and Immunopurifies Modified Peptides for Mass Spectrometry.Journal of proteome research · 2021Article
- Gulf War Illness: Mechanisms Underlying Brain Dysfunction and Promising Therapeutic Strategies.Pharmacology & therapeutics · 2021Review
- Assessment of Ketamine and Its Enantiomers in an Organophosphate-Based Rat Model for Features of Gulf War Illness.International journal of environmental research and public health · 2020Article
- Prevention of pesticide-induced neuronal dysfunction and mortality with nucleophilic poly-Oxime topical gel.Science advances · 2018Article
- Chlorpyrifos oxon promotes tubulin aggregation via isopeptide cross-linking between diethoxyphospho-Lys and Glu or Asp: Implications for neurotoxicity.The Journal of biological chemistry · 2018Article
- Trends in brain cancer mortality among U.S. Gulf War veterans: 21 year follow-up.Cancer epidemiology · 2017Article
- Review
- Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds.Frontiers in neuroscience · 2016Review
- Impact of Exposure to Fenitrothion on Vital Organs in Rats.Journal of toxicology · 2016Article
- Recent research on Gulf War illness and other health problems in veterans of the 1991 Gulf War: Effects of toxicant exposures during deployment.Cortex; a journal devoted to the study of the nervous system and behavior · 2016Review
- Neuregulin1β improves cognitive dysfunction and up-regulates expression of p-ERK1/2 in rats with chronic omethoate poisoning.Behavioral and brain functions : BBF · 2015Article
- A Chronic Longitudinal Characterization of Neurobehavioral and Neuropathological Cognitive Impairment in a Mouse Model of Gulf War Agent Exposure.Frontiers in integrative neuroscience · 2015Article
- Article
- Galantamine prevents long-lasting suppression of excitatory synaptic transmission in CA1 pyramidal neurons of soman-challenged guinea pigs.Neurotoxicology · 2014Article
- Longitudinal assessment of chlorpyrifos exposure and effect biomarkers in adolescent Egyptian agricultural workers.Journal of exposure science & environmental epidemiology · 2013Article
- Functional consequences of repeated organophosphate exposure: potential non-cholinergic mechanisms.Pharmacology & therapeutics · 2012Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Agricultural and household organophosphorus (OP) pesticides inhibit acetylcholinesterase (AchE), resulting in increased acetylcholine (Ach) in the central nervous system. In adults, acute and prolonged exposure to high doses of AchE inhibitors causes severe, clinically apparent symptoms, followed by lasting memory impairments and cognitive dysfunction. The neurotoxicity of repeated environmental exposure to lower, subclinical doses of OP pesticides in adults is not as well studied. However, repeated exposure to acetylcholinesterase inhibitors, such as chlorpyrifos (CPF), pyridostigmine, and sarin nerve agent, has been epidemiologically linked to delayed onset symptoms in Gulf War Illness and may be relevant to environmental exposure in farm workers among others. We treated adult mice with a subclinical dose (5 mg/kg) of CPF for 5 consecutive days and investigated hippocampal synaptic transmission and spine density early (2-7 days) and late (3 months) after CPF administration. No signs of cholinergic toxicity were observed at any time during or after treatment. At 2-7 days after the last injection, we found increased synaptic transmission in the CA3-CA1 region of the hippocampus of CPF-treated mice compared with controls. In contrast, at 3 months after CPF administration, we observed a 50% reduction in synaptic transmission likely due to a corresponding 50% decrease in CA1 pyramidal neuron synaptic spine density. This study is the first to identify a biphasic progression of synaptic abnormalities following repeated OP exposure and suggests that even in the absence of acute cholinergic toxicity, repeated exposure to CPF causes delayed persistent damage to the adult brain in vivo.
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Registered trials
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.