Journal of Molecular Neuroscience

, Volume 49, Issue 1, pp 172–181 | Cite as

Protective Effect of Carbamazepine on Kainic Acid-induced Neuronal Cell Death Through Activation of Signal Transducer and Activator of Transcription-3

  • Hae Jeong Park
  • Su Kang Kim
  • Joo-Ho Chung
  • Jong Woo Kim
Article

Abstract

Studies have shown that the protective effect of carbamazepine (CBZ) on seizure-induced neuronal injury. However, its precise mechanisms remain unknown. Here, to investigate the neuroprotective mechanism of CBZ against seizure-induced neuronal cell death, we identified the change of gene expressions by CBZ in the hippocampus of kainic acid (KA)-treated mice using microarray method, and studied the involvement of candidate gene in neuroprotective action of CBZ. KA (15 mg/kg) and/or CBZ (30 mg/kg, 0.5 h after KA exposure) were injected intraperitoneally into mice. Through microarray analysis, we found that signal transducer and activator of transcription-3 (Stat3) gene expression was upregulated in the hippocampal CA3 region, 24 h after KA injection (15 mg/kg), and that CBZ further elevated Stat3 expression in KA-treated mice. KA also increased the protein level and phosphorylation of Stat3, and CBZ further increased the Stat3 phosphorylation, without changing Stat3 protein level in KA-treated mice. In particular, phospho-Stat3 immunoreactivity (IR) by KA was shown in astrocytes rather than in neurons; whereas phospho-Stat3 IR by CBZ in KA-treated mice was observed predominantly in neurons, and also in neuroprotective protein Bcl-xL-expression cells. These results indicate that Stat3 may play an important role in neuroprotective action of CBZ on seizure-induced neuronal injury.

Keywords

Carbamazepine Kainic acid Seizure Signal transducer and activator of transcription-3 Neuroprotection 

Supplementary material

12031_2012_9854_MOESM1_ESM.doc (97 kb)
ESM 1(DOC 97 kb)
12031_2012_9854_MOESM2_ESM.doc (310 kb)
ESM 2(DOC 310 kb)

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Hae Jeong Park
    • 1
  • Su Kang Kim
    • 1
  • Joo-Ho Chung
    • 1
  • Jong Woo Kim
    • 2
  1. 1.Kohwang Medical Research Institute, School of MedicineKyung Hee UniversitySeoulRepublic of Korea
  2. 2.Department of Neuropsychiatry, School of MedicineKyung Hee UniversitySeoulRepublic of Korea

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