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Sodium Valproate Reduces Neuronal Apoptosis in Acute Pentylenetetrzole-Induced Seizures via Inhibiting ER Stress

Neurochemical Research volume 44, pages 2517–2526 (2019)Cite this article

Abstract

Endoplasmic reticulum (ER) stress has been indicated to be involved in the pathogenesis of epilepsy. Sodium valproate (VPA), one of the most commonly used antiepileptic drugs, is reported to regulate ER stress in many neurological diseases. However, the effect of VPA on ER stress in epilepsy remains unclear. The current study was performed to investigate the role of ER stress in the neuroprotection of VPA against seizure induced by pentylenetetrzole (PTZ). Our results showed that VPA treatment could inhibit the increased expressions of ER stress proteins (GRP78 and CHOP), and significantly reduce neuronal apoptosis in the PTZ-induced experimental seizure model. In addition, Salubrinal, an ER stress inhibitor, was used as a positive control, and exhibited neuroprotective effects via inhibiting excessive ER stress in the seizure model, which further supported that the inhibition in ER stress by VPA treatment could exert neuroprotection in seizures. In summary, our work demonstrated for the first time that ER stress was involved in the neuroprotective potential of VPA for seizures.

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Affiliations

  1. Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China

    Jie Fu & Yangmei Chen

  2. Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China

    Jie Fu

  3. Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China

    Lilei Peng, Haiping He & Shan Zeng

  4. Departments of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA

    Weijun Wang, Haiping He, Shan Zeng & Thomas C. Chen

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  1. Jie Fu
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Correspondence to Thomas C. Chen or Yangmei Chen.

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Fu, J., Peng, L., Wang, W. et al. Sodium Valproate Reduces Neuronal Apoptosis in Acute Pentylenetetrzole-Induced Seizures via Inhibiting ER Stress. Neurochem Res 44, 2517–2526 (2019). https://doi.org/10.1007/s11064-019-02870-w

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  • DOI: https://doi.org/10.1007/s11064-019-02870-w

Keywords

  • Sodium valproate
  • ER stress
  • Neuronal apoptosis
  • Pentylenetetrazole
  • Epilepsy