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.