DNA Methylation Description of Hippocampus, Cortex, Amygdala, and Blood of Drug-Resistant Temporal Lobe Epilepsy

• DOI: 10.1007/s12035-022-03180-z
• Publication Date: 2023-01-05T05:02:40Z
• Authors: Patricia Sánchez-...; Marcos Elizalde-H...; Ancor Sanz-García; Inmaculada Graner...; María De Toledo; Paloma Pulido; Marta Navas; Ana Beatriz Gago-...; Lola Alonso-Guirado; María Concepción ...; Desirée Nava-Cedeño; Francisco Abad-Sa...; Cristina Virginia...; María C. Ovejero-...
• Keywords: 0301 basic medicine; Drug Resistant Epilepsy; Drug-resistant epilepsy; Epilepsy biomarkers; Epigenetic; DNA Methylation; Amygdala; Hippocampus; DNA methylation array; Temporal Lobe; 3. Good health; 03 medical and health sciences; Epilepsy, Temporal Lobe; Epigenome-wide association study (EWAS); Humans

Epigenetic changes such as DNA methylation were observed in drug-resistant temporal lobe epilepsy (DR-TLE), a disease that affects 25-30% of epilepsy patients. The main objective is to simultaneously describe DNA methylation patterns associated with DR-TLE in hippocampus, amygdala, surrounding cortex to the epileptogenic zone (SCEZ), and peripheral blood. An Illumina Infinium MethylationEPIC BeadChip array was performed in 19 DR-TLE patients and 10 postmortem non-epileptic controls. Overall, 32, 59, and 3210 differentially methylated probes (DMPs) were associated with DR-TLE in the hippocampus, amygdala, and SCEZ, respectively. These DMP-affected genes were involved in neurotrophic and calcium signaling in the hippocampus and voltage-gated channels in SCEZ, among others. One of the hippocampus DMPs (cg26834418 (CHORDC1)) showed a strong blood-brain correlation with BECon and IMAGE-CpG, suggesting that it could be a potential surrogate peripheral biomarker of DR-TLE. Moreover, in three of the top SCEZ's DMPs (SHANK3, SBF1, and MCF2L), methylation status was verified with methylation-specific qPCR. The differentially methylated CpGs were classified in DMRs: 2 in the hippocampus, 12 in the amygdala, and 531 in the SCEZ. We identified genes that had not been associated to DR-TLE so far such as TBX5, EXOC7, and WRHN. The area with more DMPs associated with DR-TLE was the SCEZ, some of them related to voltage-gated channels. The DMPs found in the amygdala were involved in inflammatory processes. We also found a potential surrogate peripheral biomarker of DR-TLE. Thus, these results provide new insights into epigenetic modifications involved in DR-TLE.