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

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.

Methyl-CpG2-binding protein 2 mediates overlapping mechanisms across brain disorders

“…The influence of MeCP2 in epilepsy is confirmed by seizures reported in RTT and by altered MeCP2 expression (Tao et al, 2012) reported in epilepsy. In PD, under-expression of MeCP2 in dopaminergic neurons of the substantia nigra, contributes to motor deficits; the same neurons alter electrochemical and neuron development in RTT mice throughout development and into adulthood (Gantz et al, 2011).…”

Differential brain region‐specific expression of MeCP2 and BDNF in Rett Syndrome patients: a distinct grey‐white matter variation

“…Antemortem ischaemia and post mortem delay to fixation are associated with variable loss of immunoreactivity, such that the tissues can appear to have a mosaic pattern of expression. Previous studies on MeCP2 immunostaining in human brain samples reported variable and scarce or weak labelling of similar cell types [29‐36]. Difference in neuronal activity was suggested as one of the reasons behind this variable labelling [27,29].…”

“…These IHC studies in the human brain have shown a mainly nuclear localization for MeCP2. Slight cytoplasmic labelling of some neurons might be related to post‐translationally modified protein [27‐32]. Laser scanning cytometry as a quantitative method to evaluate the protein level has similarly shown the presence of cells with either low or high MeCP2 expression in different regions of the brain [33‐36].…”

Comparative DNA methylation among females with neurodevelopmental disorders and seizures identifies TAC1 as a MeCP2 target gene

“…More recently, increased MECP2 expression was detected in temporal cortex of patients with intractable temporal lobe epilepsy [41]. To determine whether TAC1 is a MeCP2 target in vivo , we performed chromatin immunoprecipitation assays in HEK cells, which express high levels of TAC1 [34,35].…”