Characterization,using comparative proteomics,of differentially expressed proteins in the hippocampus of the mesial temporal lobe of epileptic rats following treatment with valproate |
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Authors: | Wu Liwen Peng Jing Wei Chaoping Liu Gu Wang Guoli Li Kongzhao Yin Fei |
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Institution: | (1) Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People’s Republic of China; |
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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. |
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