Amino Acids

, Volume 40, Issue 1, pp 221–238

Characterization, using comparative proteomics, of differentially expressed proteins in the hippocampus of the mesial temporal lobe of epileptic rats following treatment with valproate

  • Liwen Wu
  • Jing Peng
  • Chaoping Wei
  • Gu Liu
  • Guoli Wang
  • Kongzhao Li
  • Fei Yin
Original Article

DOI: 10.1007/s00726-010-0638-8

Cite this article as:
Wu, L., Peng, J., Wei, C. et al. Amino Acids (2011) 40: 221. doi:10.1007/s00726-010-0638-8

Abstract

The objective of the study was to explore the pathogenesis of mesial temporal lobe epilepsy (MTLE) and the mechanism of valproate administration in the early stage of MTLE development. We performed a global comparative analysis and function classification of differentially expressed proteins using proteomics. MTLE models of developmental rats were induced by lithium-pilocarpine. Proteins in the hippocampus were separated by 2-DE technology. PDQuest software was used to analyze 2-DE images, and MALDI-TOF-MS was used to identify the differentially expressed proteins. Western blot was used to determine the differential expression levels of synapse-related proteins synapsin-1, dynamin-1 and neurogranin in both MTLE rat and human hippocampus. A total of 48 differentially expressed proteins were identified between spontaneous and non-spontaneous MTLE rats, while 41 proteins between MTLE rats and post valproate-treatment rats were identified. All of the proteins can be categorized into several groups by biological functions: synaptic and neurotransmitter release, cytoskeletal structure and dynamics, cell junctions, energy metabolism and mitochondrial function, molecular chaperones, signal regulation and others. Western blot results were similar to the changes noted in 2-DE. The differentially expressed proteins, especially the proteins related to synaptic and neurotransmitter release function, such as synapsin-1, dynamin-1 and neurogranin, are probably involved in the mechanism of MTLE and the pharmacological effect of valproate. These findings may provide important clues to elucidate the mechanism of chronic MTLE and to identify an optimum medication intervention time and new biomarkers for the development of pharmacological therapies targeted at epilepsy.

Keywords

Mesial temporal lobe epilepsyHippocampusValproateProteomicsMechanism

Abbreviations

AEDs

Antiepileptic drugs

Cx50

Gap junction channel protein connexin 50

2-DE

Two-dimensional polyacrylamide gel electrophoresis

F-actin

Actin filaments

HSPs

Heat shock proteins

IML

Inner molecular layer

MALDI-TOF-MS

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

MAPKK1

Dual specificity mitogen-activated protein kinase kinase 1

MTLE

Mesial temporal lobe epilepsy

SE

Status epilepticus

SIR2-like

NAD-dependent deacetylase sirtuin-2

TCP-1

T-complex protein 1

VPA

Valproate

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Liwen Wu
    • 1
  • Jing Peng
    • 1
  • Chaoping Wei
    • 1
  • Gu Liu
    • 1
  • Guoli Wang
    • 1
  • Kongzhao Li
    • 1
  • Fei Yin
    • 1
  1. 1.Department of PediatricsXiangya Hospital, Central South UniversityChangshaPeople’s Republic of China