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Background and Aims: DNA methylation and demethylation play a crucial role in the regulation of gene expression, though their interplay during pathogenesis of hippocampal scelerosis (HS) remains elusive. The present study was designed to investigate the DNA methylation regulated changes in expression of HS patients.Methods: We performed integrative analysis of genome-wide CpG-DNA methylation profiling and RNA sequencing to profile global changes in promoter methylation and gene expression in HS patients. Real time PCR was performed to validate the findings of methylation and RNA sequencing.Results: A total of 16040 sites showed altered DNA methylation in all the CpG islands. Of these, 3185 sites were in the promoter regions, of which 66 genes showed an inverse correlation between methylation and expression. These genes are largely related to pathways predicted to participate in axon guidance by semaphorins, MAPK, ionotropic glutamate receptor pathway, notch signaling, regulatory activities related to TFAP2A and immune response, with the most distinct ones included TFAP2A, NRP1, SEMA3B, CACNG2, MAP3K11, and ADAM17.Conclusion: We performed integrated analysis of genomic methylation signature and differential gene expression patterns of hippocampal tissues resected from patients with HS for the first time. Collectively, our findings implicate DNA methylation as a critical regulator of the pathogenic mechanisms of epileptogenesis associated with HS. [ABSTRACT FROM AUTHOR]

Aim: This study is focused on GABRG2 gene sequence variations in patients with mesial temporal lobe epilepsy (mTLE). The GABAA receptor is a heteropentameric receptor and alpha-1 beta-2 gamma-2 subunits combination is most abundant and present in almost all regions of the brain. The gamma-2 subunit (GABRG2) gene mutations have been reported in different epilepsy pathologies. In the present study we have looked for GABRG2 gene sequence variations in patients with mTLE. Materials and Methods: Twenty patients (12 females and eight males, age 4.6-38 years) with MTLE were recruited for this investigation. Patients were recommended for epilepsy surgery after all clinical investigations as per the epilepsy protocol. Ethnically matched glioma or meningioma patients were considered as nonepileptic controls. During temporal lobectomy of amygdalohippocampectomy, hippocampal brain tissue samples were resected guided by intraoperative electrocorticography (ECoG) activity. All 11 exons of GABRG2 gene with their flanking intronic regions were amplified by polymerase chain reaction (PCR) and screened by DNA sequencing analysis for sequence variations. Statistical Analysis Used: Comparison of allele frequencies between patient and control groups was determined using a χ2 test. Results and Conclusions: Total five DNA sequence variations were identified, three in exonic regions (c.643A > G, rs211035), (c.T > A, rs424740), and (c.C > T, rs418210) and two in intronic regions (c.751 + 41A > G, rs211034) and (c.751 + 52G > A, rs 34281163). Allele frequencies of variants identified in this study did not differ between patients and normal controls. Thus, we conclude that GABRG2 gene may not be playing significant role in the development of epilepsy or as a susceptibility gene in patients with MTLE in Indian population. [ABSTRACT FROM AUTHOR]

Accurate localization of the "epileptogenic zone (EZ)" is an important issue in epilepsy surgery. The EZ is not discrete and focal; in fact, the epileptogenic networks can spread ictal activity to different regions of the brain. Changes in network characteristics and functional connectivity are shown to be associated with epilepsy. Seizures are thought to represent a hyper-synchronous state and presumable changes in synchronization between different brain regions underlie the mechanisms of seizure spread. Although presurgical evaluation of the epileptogenic network analysis can be carried out using existing investigative techniques like electroencephalogram (EEG), video-EEG, magnetic resonance imaging, single-photon emission computed tomography, and magnetoencephalography, advanced imaging techniques such as optical intrinsic spectroscopy, auto-fluorescence imaging, voltage sensitive dye imaging, and calcium imaging have the advantage of better spatiotemporal resolution over a large area of cortex. Understanding the wide-scale dynamic networks by analyzing the changes in the synchronization patterns using advanced imaging techniques will be instrumental in the presurgical analysis of the epileptogenic network and better localization of the EZs in the future. [ABSTRACT FROM AUTHOR]