2. Academic Validation
  3. Permethrin induces epileptic susceptibility via activation of Na+ channels and rise in glutamate

Permethrin induces epileptic susceptibility via activation of Na+ channels and rise in glutamate

  • Commun Biol. 2025 Nov 24;8(1):1644. doi: 10.1038/s42003-025-09037-0.
Ming Su 1 2,  Yuansong Zhang 3 4 5 6,  Zhi Feng 1 2,  Wei Li 6,  Yuan Liu 7,  Cenglin Xu 8,  Congjian Zhao 9,  Patrick Kwan 10 11 12,  Xin Tian 13 14 15 16,  Li Li 17 18
Affiliations

Affiliations

  • 1 Research Center of Stem Cells and Ageing, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, China.
  • 2 Chongqing School, University of Chinese Academy of Sciences, Chongqing, China.
  • 3 Department of Geriatrics, Laboratory of Research and Translation for Geriatric Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 4 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Major Neurological and Mental Disorders, Chongqing, China.
  • 5 Department of Epilepsy Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 6 Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing Medical University, Chongqing, China.
  • 7 Key Laboratory of Reservoir Aquatic Environment, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, China.
  • 8 Department of Neurology, Zhejiang Provincial Hospital of Chinese Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
  • 9 Research Center of Biomedical Engineering, School of Life Health Information Science and Engineering, Chongqing University of Posts and Telecommunications, Chongqing, China.
  • 10 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Major Neurological and Mental Disorders, Chongqing, China. [email protected].
  • 11 Department of Epilepsy Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [email protected].
  • 12 Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia. [email protected].
  • 13 Department of Geriatrics, Laboratory of Research and Translation for Geriatric Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [email protected].
  • 14 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Major Neurological and Mental Disorders, Chongqing, China. [email protected].
  • 15 Department of Epilepsy Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [email protected].
  • 16 Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing Medical University, Chongqing, China. [email protected].
  • 17 Research Center of Stem Cells and Ageing, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, China. [email protected].
  • 18 Chongqing School, University of Chinese Academy of Sciences, Chongqing, China. [email protected].
PMID: 41286411 DOI: 10.1038/s42003-025-09037-0
Abstract

Permethrin, a common pyrethroid Insecticide, is extensively used to control insect pests and has been widely detected in the environment. A growing body of epidemiological studies has revealed a substantial increase in the prevalence of epilepsy among individuals highly exposed to pesticides. However, the mechanism of action of permethrin in epilepsy remains elusive. In this study, we investigate the effects of permethrin on zebrafish and mice exposed to environmentally relevant concentrations. Acute exposure to permethrin induces dose-dependent epileptiform symptoms in zebrafish, including whirlpool-like movement, clonus-like convulsions, nystagmus and neuronal hyperactivity. Extended exposure results in neuronal hyperexcitation, impaired neurogenesis and enhanced glial cell hyperplasia in zebrafish. Additionally, pre-exposure to permethrin significantly increases susceptibility to seizures in mice. Mechanistically, the effects of permethrin are conserved across different species, promoting the activation of sodium ion channels, particularly Nav1.6. This activation increases glutamate levels, which play a critical role in epileptiform symptoms. Our findings suggest that permethrin exposure leads to the activation of sodium ion channels and disrupts the balance between excitatory versus inhibitory neurotransmitters, resulting in seizure-like symptoms and increased susceptibility to epilepsy. Sodium channels and neurotransmitter balance may be protective targets against permethrin exposure.

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