Acute Paraoxon-Induced Neurotoxicity in a Mouse Survival Model: Oxidative Stress, Dopaminergic System Alterations and Memory Deficits

Edurne Urquizu, Selma Paratusic, Júlia Goyenechea, Cristian Gómez-Canela, Berta Fumàs, David Pubill, Demetrio Raldúa, Jordi Camarasa, Elena Escubedo, Raúl López-Arnau*

*Corresponding author for this work

Research output: Indexed journal article Articlepeer-review

Abstract

The secondary neurotoxicity induced by severe organophosphorus (OP) poisoning, including paraoxon (POX), is associated with cognitive impairments in survivors, who, despite receiving appropriate emergency treatments, may still experience lasting neurological deficits. Thus, the present study provides a survival mouse model of acute and severe POX poisoning to examine secondary neurotoxicity. Swiss CD-1 male mice were injected with POX (4 mg/kg, s.c.) followed by atropine (4 mg/kg, i.p.), pralidoxime (2-PAM; Pyridine-2-aldoxime methochloride) (25 mg/kg, i.p., twice, 1 h apart) and diazepam (5 mg/kg, i.p.), resulting in a survival rate >90% and Racine score of 5–6. Our results demonstrated that the model showed increased lipid peroxidation, downregulation of antioxidant enzymes and astrogliosis in the mouse hippocampus (HP) and prefrontal cortex (PFC), brain areas involved in cognitive functions. Moreover, dopamine (DA) levels were reduced in the hp, but increased in the PFC. Furthermore, the survival mouse model of acute POX intoxication did not exhibit phenotypic manifestations of depression, anxiety or motor incoordination. However, our results demonstrated long-term recognition memory impairments, which are in accordance with the molecular and neurochemical effects observed. In conclusion, this mouse model can aid in researching POX exposure’s effects on memory and developing potential countermeasures against the secondary neurotoxicity induced by severe OP poisoning.

Original languageEnglish
Article number12248
Number of pages18
JournalInternational Journal of Molecular Sciences
Volume25
Issue number22
DOIs
Publication statusPublished - Nov 2024

Keywords

  • memory
  • mouse
  • organophosphate
  • oxidative stress
  • paraoxon

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