Effects of MeCP2 on chronic seizures and cognitive function in mice with temporal lobe epilepsy

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research Pub Date : 2025-02-01 DOI:10.1016/j.eplepsyres.2025.107512

Yu Chen , Shu-Nan Yang , Guan-Ling Fu , Xiao-Xuan Liu , Xin-Li Xiao , Xiao-Lin Wu , Feng Wu , Yan-Bing Ma , Sheng-Feng Ji , Jin-Song Zhou , Jian-Xin Liu

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引用次数: 0

Abstract

Mutations in methyl CpG binding protein 2 (MeCP2) are linked to Rett syndrome, in which epilepsy is one of the most well-described disorders. However, little is known about the specific role of MeCP2 during epileptogenesis. Our previous study has demonstrated that MeCP2 has a unique control on the development of mossy fiber sprouting (MFS) in the epileptic hippocampus. This study aimed to (1) examine whether MeCP2 affects spontaneous recurrent seizures (SRSs) and cognitive deficits in mice with pilocarpine-induced epilepsy, and (2) profile MeCP2’s downstream molecular events. In the dentate gyrus (DG), we found that over-expression or suppression of MeCP2 significantly reduced or increased the frequency, duration, and number of stage 5 seizures of SRSs during the chronic stage after the SE. Over-expression of MeCP2 improved cognitive deficits in TLE mice, while exacerbated cognitive performances were observed following MeCP2 knockdown. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA-sequence analyses revealed that MeCP2-targeted genes have far‑reaching impacts on the pathophysiological events during epileptogenesis, including neuron differentiation, neurogenesis, axon guidance, and so on.

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来源期刊

Epilepsy Research 医学-临床神经学

CiteScore

0.10

自引率

4.50%

发文量

143

审稿时长

62 days

期刊介绍： Epilepsy Research provides for publication of high quality articles in both basic and clinical epilepsy research, with a special emphasis on translational research that ultimately relates to epilepsy as a human condition. The journal is intended to provide a forum for reporting the best and most rigorous epilepsy research from all disciplines ranging from biophysics and molecular biology to epidemiological and psychosocial research. As such the journal will publish original papers relevant to epilepsy from any scientific discipline and also studies of a multidisciplinary nature. Clinical and experimental research papers adopting fresh conceptual approaches to the study of epilepsy and its treatment are encouraged. The overriding criteria for publication are novelty, significant clinical or experimental relevance, and interest to a multidisciplinary audience in the broad arena of epilepsy. Review articles focused on any topic of epilepsy research will also be considered, but only if they present an exceptionally clear synthesis of current knowledge and future directions of a research area, based on a critical assessment of the available data or on hypotheses that are likely to stimulate more critical thinking and further advances in an area of epilepsy research.