Unveiling Molecular Dynamics of MeCp2, CDKL5 and BDNF in the Hippocampus of Individuals With Intractable Mesial Temporal Lobe Epilepsy

Abstract

Mutations occurring in the MeCp2, CDKL5 and BDNF genes have been linked to epileptogenesis in various epilepsy syndromes. This study employed bioinformatics analysis of transcriptomic data to examine the interrelationship among these genes in both epileptic and healthy individuals. Moreover, we assessed the expression of MeCp2, CDKL5 and BDNF at both mRNA and protein levels in human hippocampal tissues obtained from 22 patients undergoing epilepsy surgery for mesial temporal lobe epilepsy (MTLE) as well as from 25 autopsied specimens. Bioinformatics findings suggest that MeCp2, CDKL5 and BDNF genes play a role in regulating genes associated with epilepsy and disruptions in these genes may contribute to epilepsy development. Furthermore, the study reveals significantly lower MeCp2 and CDKL5 protein levels in the epileptic hippocampus compared to controls. Positive correlations are observed between MeCp2 and CDKL5 mRNA expression in autopsied samples and between CDKL5 and BDNF mRNA expression in epileptic hippocampal tissues. Differences in mRNA expression correlation patterns of MeCp2 and CDKL5 with BDNF are found between epileptic and control hippocampal tissues. Moreover, a significant positive correlation between MeCp2 and CDKL5 protein expression is noted in control hippocampal tissues. Our data suggest that altered expression of MeCp2, CDKL5 and BDNF within the hippocampus may contribute to epileptogenic processes in MTLE, impacting seizure characteristics, surgical outcomes and responses to antiepileptic drugs. Alterations in the expression of MeCp2, CDKL5 and BDNF within the hippocampus might contribute to the epileptogenic processes in MTLE. These changes could be linked to distinct functional consequences in epilepsy.