Effects of valproate sodium on extracellular signal‑regulated kinase 1/2 phosphorylation following hippocampal neuronal epileptiform discharge in rats

Xu,Zucai; Zhang,Jun; Lei,Xianze; Xu,Zhongxiang; Peng,Yan; Yao,Benhai; Xu,Ping

doi:10.3892/etm.2013.1343

Effects of valproate sodium on extracellular signal‑regulated kinase 1/2 phosphorylation following hippocampal neuronal epileptiform discharge in rats

Authors:
- Zucai Xu
- Jun Zhang
- Xianze Lei
- Zhongxiang Xu
- Yan Peng
- Benhai Yao
- Ping Xu
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Affiliations: Department of Neurology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China
Published online on: October 11, 2013 https://doi.org/10.3892/etm.2013.1343
Pages: 1397-1401

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Abstract

The aim of the present study was to investigate the effects of valproate sodium (VPAS) on the phosphorylation extracellular signal‑regulated kinase 1/2 (ERK1/2) following hippocampal neuronal epileptiform discharge in rat neurons. The study used neurons from female and male neonate Sprague‑Dawley (SD) rats (at least 24 h old), which were rapidly decapitated. Following the successful development of the epileptiform discharge cell model, the neurons were divided into two groups, the VPAS group and the control group. In the concentration‑response experiment, the neurons were incubated with three different concentrations of VPAS (50, 75 and 100 mg/l) 30 min prior to the epileptiform discharge. The expression of phosphorylated ERK1/2 (p‑ERK1/2) was examined using an immunofluorescence technique. In the time‑response experiment, the neurons were incubated with VPAS (50 mg/l) and monitored at different time‑points (30 min prior to the epileptiform discharge and 0 min, 30 min, 2 h and 6 h subsequent to epileptiform discharge), and western blotting was employed to measure the changes in p‑ERK1/2 protein expression. No significant differences in the expression of p‑ERK1/2 among the neurons treated with different concentrations of VPAS were identified in the concentration‑response experiment. However, in the time‑response experiment, the expression of p‑ERK1/2 30 min prior to the epileptiform discharge was significantly lower compared with that at the other time‑points. Furthermore, 50 mg/l VPAS was capable of decreasing the action potential frequency of the neuronal epileptiform discharge. ERK1/2 was excessively and persistently activated following the epileptiform discharge of the neurons. In addition, a low concentration of VPAS was effective at inhibiting the phosphorylation of ERK1/2 at an earlier period of neuronal epileptiform discharge.

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