Sánchez Jiménez, PatriciaElizalde-Horcada, MarcosSanz García, AncorGranero Cremades, InmaculadaToledo, María dePullido, PalomaNavas, MartaGago-Veiga, BeatrizAlonso-Guirado, LolaAlonso Cerezo, María ConcepciónNava Cedeño, DesirééAbad Santos, FranciscoTorres Díaz, Cristina VirginiaOvejero Benito, María del CarmenUniversidad San Pablo-CEU. Facultad de Farmacia. Departamento de Ciencias Farmacéuticas y de la Salud2024-01-172024-01-172023-01-05Sánchez-Jiménez, P., Elizalde-Horcada, M., Sanz-García, A. et al. DNA Methylation Description of Hippocampus, Cortex, Amygdala, and Blood of Drug-Resistant Temporal Lobe Epilepsy. Mol Neurobiol 60, 2070–2085 (2023). https://doi.org/10.1007/s12035-022-03180-z1559-1182http://hdl.handle.net/10637/14941Epigenetic changes such as DNA methylation were observed in drug-resistant temporal lobe epilepsy (DR-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. Methods: An Illumina Infinium MethylationEPIC BeadChip array was performed in 19 DR-TLE patients and 10 postmortem non-epileptic controls. Results: Overall, 32, 59, and 3210 differentially methylated probes (DMPs) were associated with DR-TLE in the hippocampus, amygdala, and SCEZ, respectively. These DMPs 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. Conclusion: 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..application/pdfenopen accessDNA methylation arrayDrug-resistant epilepsyEpigenome-wide association study (EWAS)Epilepsy biomarkersEpigeneticArtículo10.1007/s12035-022-03180-zhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es