PUBLICATION
Organophosphorus diisopropylfluorophosphate (DFP) intoxication in zebrafish larvae causes behavioral defects, neuronal hyperexcitation and neuronal death
- Authors
- Brenet, A., Somkhit, J., Hassan-Abdi, R., Yanicostas, C., Romain, C., Bar, O., Igert, A., Saurat, D., Taudon, N., Dal-Bo, G., Nachon, F., Dupuis, N., Soussi-Yanicostas, N.
- ID
- ZDB-PUB-201120-47
- Date
- 2020
- Source
- Scientific Reports 10: 19228 (Journal)
- Registered Authors
- Soussi-Yanicostas, Nadia
- Keywords
- none
- MeSH Terms
-
- Acetylcholinesterase/metabolism
- Animals
- Apoptosis/drug effects
- Behavior, Animal/drug effects*
- Brain/drug effects
- Brain/metabolism
- Calcium/metabolism
- Cell Death/drug effects*
- Isoflurophate/toxicity*
- Larva/drug effects*
- Neurons/drug effects*
- Neurons/metabolism
- Organophosphate Poisoning/complications
- Organophosphate Poisoning/metabolism*
- Seizures/etiology
- Seizures/metabolism
- Zebrafish
- PubMed
- 33154418 Full text @ Sci. Rep.
Citation
Brenet, A., Somkhit, J., Hassan-Abdi, R., Yanicostas, C., Romain, C., Bar, O., Igert, A., Saurat, D., Taudon, N., Dal-Bo, G., Nachon, F., Dupuis, N., Soussi-Yanicostas, N. (2020) Organophosphorus diisopropylfluorophosphate (DFP) intoxication in zebrafish larvae causes behavioral defects, neuronal hyperexcitation and neuronal death. Scientific Reports. 10:19228.
Abstract
With millions of intoxications each year and over 200,000 deaths, organophosphorus (OP) compounds are an important public health issue worldwide. OP poisoning induces cholinergic syndrome, with respiratory distress, hypertension, and neuron damage that may lead to epileptic seizures and permanent cognitive deficits. Existing countermeasures are lifesaving but do not prevent long-lasting neuronal comorbidities, emphasizing the urgent need for animal models to better understand OP neurotoxicity and identify novel antidotes. Here, using diisopropylfluorophosphate (DFP), a prototypic and moderately toxic OP, combined with zebrafish larvae, we first showed that DFP poisoning caused major acetylcholinesterase inhibition, resulting in paralysis and CNS neuron hyperactivation, as indicated by increased neuronal calcium transients and overexpression of the immediate early genes fosab, junBa, npas4b, and atf3. In addition to these epileptiform seizure-like events, DFP-exposed larvae showed increased neuronal apoptosis, which were both partially alleviated by diazepam treatment, suggesting a causal link between neuronal hyperexcitation and cell death. Last, DFP poisoning induced an altered balance of glutamatergic/GABAergic synaptic activity with increased NR2B-NMDA receptor accumulation combined with decreased GAD65/67 and gephyrin protein accumulation. The zebrafish DFP model presented here thus provides important novel insights into the pathophysiology of OP intoxication, making it a promising model to identify novel antidotes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping