Proteomic Analysis Reveals the Vital Role of Synaptic Plasticity in the Pathogenesis of Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) is a chronic neurological disorder that is often resistant to antiepileptic drugs. The pathogenesis of TLE is extremely complicated and remains elusive. Understanding the molecular mechanisms underlying TLE is crucial for its diagnosis and treatment. In the present study...

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Main Authors: Xu Qian, Ji-Qiang Ding, Xin Zhao, Xin-Wen Sheng, Zhao-Rui Wang, Qi-xing Yang, Jing-Jun Zheng, Jia-Gui Zhong, Teng-Yue Zhang, Shu-Qiao He, Wei-Dong Ji, Wei Li, Mei Zhang
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2022/8511066
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author Xu Qian
Ji-Qiang Ding
Xin Zhao
Xin-Wen Sheng
Zhao-Rui Wang
Qi-xing Yang
Jing-Jun Zheng
Jia-Gui Zhong
Teng-Yue Zhang
Shu-Qiao He
Wei-Dong Ji
Wei Li
Mei Zhang
author_facet Xu Qian
Ji-Qiang Ding
Xin Zhao
Xin-Wen Sheng
Zhao-Rui Wang
Qi-xing Yang
Jing-Jun Zheng
Jia-Gui Zhong
Teng-Yue Zhang
Shu-Qiao He
Wei-Dong Ji
Wei Li
Mei Zhang
author_sort Xu Qian
collection DOAJ
description Temporal lobe epilepsy (TLE) is a chronic neurological disorder that is often resistant to antiepileptic drugs. The pathogenesis of TLE is extremely complicated and remains elusive. Understanding the molecular mechanisms underlying TLE is crucial for its diagnosis and treatment. In the present study, a lithium-pilocarpine-induced TLE model was employed to reveal the pathological changes of hippocampus in rats. Hippocampal samples were taken for proteomic analysis at 2 weeks after the onset of spontaneous seizure (a chronic stage of epileptogenesis). Isobaric tag for relative and absolute quantization (iTRAQ) coupled with liquid chromatography-tandem mass spectrometry (LC–MS/MS) technique was applied for proteomic analysis of hippocampus. A total of 4173 proteins were identified from the hippocampi of epileptic rats and its control, of which 27 differentially expressed proteins (DEPs) were obtained with a fold change>1.5 and P<0.05. Bioinformatics analysis indicated 27 DEPs were mainly enriched in “regulation of synaptic plasticity and structure” and “calmodulin-dependent protein kinase activity,” which implicate synaptic remodeling may play a vital role in the pathogenesis of TLE. Consequently, the synaptic plasticity-related proteins and synaptic structure were investigated to verify it. It has been demonstrated that CaMKII-α, CaMKII-β, and GFAP were significant upregulated coincidently with proteomic analysis in the hippocampus of TLE rats. Moreover, the increased dendritic spines and hippocampal sclerosis further proved that synaptic plasticity involves in the development of TLE. The present study may help to understand the molecular mechanisms underlying epileptogenesis and provide a basis for further studies on synaptic plasticity in TLE.
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spelling doaj-art-646d5ac1f53b4a5bad781a5d16939f5d2025-02-03T06:04:49ZengWileyNeural Plasticity1687-54432022-01-01202210.1155/2022/8511066Proteomic Analysis Reveals the Vital Role of Synaptic Plasticity in the Pathogenesis of Temporal Lobe EpilepsyXu Qian0Ji-Qiang Ding1Xin Zhao2Xin-Wen Sheng3Zhao-Rui Wang4Qi-xing Yang5Jing-Jun Zheng6Jia-Gui Zhong7Teng-Yue Zhang8Shu-Qiao He9Wei-Dong Ji10Wei Li11Mei Zhang12Department of Clinical PharmacologyDepartment of NeurosurgeryDepartment of Clinical PharmacologyDepartment of Clinical PharmacologyDepartment of NeurosurgeryDepartment of Clinical PharmacologyDepartment of Clinical PharmacologyDepartment of NeurosurgeryDepartment of Clinical PharmacologyDepartment of Clinical PharmacologyCenter for Translational MedicineDepartment of NeurosurgeryDepartment of Clinical PharmacologyTemporal lobe epilepsy (TLE) is a chronic neurological disorder that is often resistant to antiepileptic drugs. The pathogenesis of TLE is extremely complicated and remains elusive. Understanding the molecular mechanisms underlying TLE is crucial for its diagnosis and treatment. In the present study, a lithium-pilocarpine-induced TLE model was employed to reveal the pathological changes of hippocampus in rats. Hippocampal samples were taken for proteomic analysis at 2 weeks after the onset of spontaneous seizure (a chronic stage of epileptogenesis). Isobaric tag for relative and absolute quantization (iTRAQ) coupled with liquid chromatography-tandem mass spectrometry (LC–MS/MS) technique was applied for proteomic analysis of hippocampus. A total of 4173 proteins were identified from the hippocampi of epileptic rats and its control, of which 27 differentially expressed proteins (DEPs) were obtained with a fold change>1.5 and P<0.05. Bioinformatics analysis indicated 27 DEPs were mainly enriched in “regulation of synaptic plasticity and structure” and “calmodulin-dependent protein kinase activity,” which implicate synaptic remodeling may play a vital role in the pathogenesis of TLE. Consequently, the synaptic plasticity-related proteins and synaptic structure were investigated to verify it. It has been demonstrated that CaMKII-α, CaMKII-β, and GFAP were significant upregulated coincidently with proteomic analysis in the hippocampus of TLE rats. Moreover, the increased dendritic spines and hippocampal sclerosis further proved that synaptic plasticity involves in the development of TLE. The present study may help to understand the molecular mechanisms underlying epileptogenesis and provide a basis for further studies on synaptic plasticity in TLE.http://dx.doi.org/10.1155/2022/8511066
spellingShingle Xu Qian
Ji-Qiang Ding
Xin Zhao
Xin-Wen Sheng
Zhao-Rui Wang
Qi-xing Yang
Jing-Jun Zheng
Jia-Gui Zhong
Teng-Yue Zhang
Shu-Qiao He
Wei-Dong Ji
Wei Li
Mei Zhang
Proteomic Analysis Reveals the Vital Role of Synaptic Plasticity in the Pathogenesis of Temporal Lobe Epilepsy
Neural Plasticity
title Proteomic Analysis Reveals the Vital Role of Synaptic Plasticity in the Pathogenesis of Temporal Lobe Epilepsy
title_full Proteomic Analysis Reveals the Vital Role of Synaptic Plasticity in the Pathogenesis of Temporal Lobe Epilepsy
title_fullStr Proteomic Analysis Reveals the Vital Role of Synaptic Plasticity in the Pathogenesis of Temporal Lobe Epilepsy
title_full_unstemmed Proteomic Analysis Reveals the Vital Role of Synaptic Plasticity in the Pathogenesis of Temporal Lobe Epilepsy
title_short Proteomic Analysis Reveals the Vital Role of Synaptic Plasticity in the Pathogenesis of Temporal Lobe Epilepsy
title_sort proteomic analysis reveals the vital role of synaptic plasticity in the pathogenesis of temporal lobe epilepsy
url http://dx.doi.org/10.1155/2022/8511066
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