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Up-Regulated Methyl CpG Binding Protein-2 in Intractable Temporal Lobe Epilepsy Patients and a Rat Model

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Abstract

Methyl CpG binding protein-2 (MeCP2) is a multifunctional nuclear protein, and regulates dendritic morphology, synaptic transmission, spontaneous neurotransmission, and short-term synaptic plasticity in the central nervous system. This study was designed to investigate the expression of MeCP2 mRNA and protein in intractable temporal lobe epilepsy (TLE) patients and an experimental animal model. MeCP2 expression was detected in 35 temporal neocortex tissue samples from patients with intractable TLE and 14 histologically normal temporal lobe tissue samples from trauma patients without epilepsy by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry and double-label immunofluorescence. In addition, the timing of MeCP2 expression was evaluated in the hippocampus and adjacent cortex of lithium chloride/pilocarpine-induced TLE rats and uninduced controls. MeCP2 was found to be expressed mainly in the nuclei of neurons, and not expressed in astrocytes. MeCP2 expression was significantly higher in the TLE patients and rats than in the control groups. Following seizures in the rat model, MeCP2 expression gradually increased in the hippocampus and adjacent cortex during the acute period (days 1 and 2) and the latent period (days 7 and 14), but decreased during the chronic period (days 30 and 60). Up-regulated expression of MeCP2 in intractable TLE patients and experimental animals suggested that MeCP2 may be involved in the pathogenesis of TLE.

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Abbreviations

AEDs:

Antiepileptic drugs

CNS:

Central nervous system

CREB:

cAMP response element-binding protein

CT:

Computed tomography

EEG:

Electroencephalogram

FITC:

Fluorescein isothiocyanate

GFAP:

Glial fibrillary acidic protein

GluR2:

Glutamate receptor 2

HDACs:

Histone deacetylases

IE:

Intractable epilepsy

i.p.:

Intraperitoneal

LiCl:

Lithium chloride

LTD:

Long-term depression

LTP:

Long-term potentiation

MBD:

Methyl-CpG-binding domain

MeCP2:

Methyl CpG binding protein-2

MFS:

Mossy fiber sprouting

MRI:

Magnetic resonance imaging

Neun:

Neuron nuclei

NSE:

Neuron-specific enolase

PI:

Propidium iodide

RT-PCR:

Reverse transcription polymerase chain reaction

RTT:

Rett syndrome

SABC:

Streptavidin biotin complex

TLE:

Temporal lobe epilepsy

TRD:

Transcriptional repression domain

TRITC:

Tetramethylrhodamine isothiocyanate

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Acknowledgments

This work was supported by a grant from the Key Project of Chongqing Municipal Health Bureau for Medical Research (No. 2010-1-36) and the National Natural Science Foundation of China (No. 81171225). The authors sincerely thank the Beijing Tiantan Hospital, Xuanwu Hospital of Capital University of Medical Sciences, and Xin-hua Hospital of Hubei for supplying the brain tissues used in this study, the patients and their families for their participation in this study, and the National Board of the Medical Affairs and the local ethics committee.

Conflict of interest

The authors declare that they have no conflict of interests regarding the publication of this study.

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Authors and Affiliations

  1. Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing, 400010, China

    Shuxin Tao, Xiaolan Yang, Yangmei Chen, Zhanqin Xiao, Heng Wang & Xing Wang

  2. Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, China

    Xuefeng Wang & Qisi Wu

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  1. Shuxin Tao
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  2. Xiaolan Yang
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Correspondence to Yangmei Chen.

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Shuxin Tao and Xiaolan Yang contributed equally to this work.

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Tao, S., Yang, X., Chen, Y. et al. Up-Regulated Methyl CpG Binding Protein-2 in Intractable Temporal Lobe Epilepsy Patients and a Rat Model. Neurochem Res 37, 1886–1897 (2012). https://doi.org/10.1007/s11064-012-0804-3

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  • DOI: https://doi.org/10.1007/s11064-012-0804-3

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