Meshkinkhood NoorMohammad, Barati Dowom Parastoo, Noorbakhsh Farshid, Ghadipasha Masoud, Gharehdaghi Jaber, Kellinghaus Christoph, Speckmann Erwin-Joseph, Khaleghi Ghadiri Maryam, Stummer Walter, Gorji Ali
Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.
Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran.
J Cell Mol Med. 2025 Feb;29(3):e70373. doi: 10.1111/jcmm.70373.
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.
甲基化CpG结合蛋白2（MeCp2）、周期蛋白依赖性激酶样5（CDKL5）和脑源性神经营养因子（BDNF）基因发生的突变与多种癫痫综合征的癫痫发生有关。本研究采用转录组数据的生物信息学分析方法，来检测癫痫患者和健康个体中这些基因之间的相互关系。此外，我们评估了从22例因内侧颞叶癫痫（MTLE）接受癫痫手术的患者以及25份尸检标本中获取的人类海马组织中MeCp2、CDKL5和BDNF在mRNA和蛋白质水平的表达。生物信息学研究结果表明，MeCp2、CDKL5和BDNF基因在调控与癫痫相关的基因中发挥作用，这些基因的破坏可能会导致癫痫的发展。此外，研究发现癫痫海马中MeCp2和CDKL5蛋白水平显著低于对照组。在尸检样本中观察到MeCp2和CDKL5 mRNA表达之间呈正相关，在癫痫海马组织中CDKL5和BDNF mRNA表达之间呈正相关。在癫痫和对照海马组织之间发现了MeCp2和CDKL5与BDNF的mRNA表达相关模式的差异。此外，在对照海马组织中MeCp2和CDKL5蛋白表达之间存在显著正相关。我们的数据表明，海马内MeCp2、CDKL5和BDNF表达的改变可能导致MTLE的癫痫发生过程，影响癫痫发作特征、手术结果和对抗癫痫药物的反应。海马内MeCp2、CDKL5和BDNF表达改变可能导致MTLE的癫痫发生过程。这些变化可能与癫痫中不同的功能后果有关。
