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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.

Titel:	DNA Methylation Description of Hippocampus, Cortex, Amygdala, and Blood of Drug-Resistant Temporal Lobe Epilepsy.
Autor/in / Beteiligte Person:	Sánchez-Jiménez, P ; Elizalde-Horcada, M ; Sanz-García, A ; Granero-Cremades, I ; De Toledo, M ; Pulido, P ; Navas, M ; Gago-Veiga, AB ; Alonso-Guirado, L ; Alonso-Cerezo, MC ; Nava-Cedeño, D ; Abad-Santos, F ; Torres-Díaz, CV ; Ovejero-Benito, MC
Link:	View record at Springer (Volltext)
Zeitschrift:	Molecular neurobiology, Jg. 60 (2023-04-01), Heft 4, S. 2070-2085
Veröffentlichung:	Clifton, NJ : Humana Press, c1987-, 2023
Medientyp:	academicJournal
ISSN:	1559-1182 (electronic)
DOI:	10.1007/s12035-022-03180-z
Schlagwort:	Humans DNA Methylation Temporal Lobe Hippocampus Amygdala Epilepsy, Temporal Lobe genetics Drug Resistant Epilepsy genetics
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Mol Neurobiol] 2023 Apr; Vol. 60 (4), pp. 2070-2085. <i>Date of Electronic Publication: </i>2023 Jan 05. MeSH Terms: Epilepsy, Temporal Lobe* / genetics ; Drug Resistant Epilepsy* / genetics ; Humans ; DNA Methylation ; Temporal Lobe ; Hippocampus ; Amygdala References: Amin U, Benbadis SR (2020) Avoiding complacency when treating uncontrolled seizures: why and how? Expert Rev Neurother 1–9. https://doi.org/10.1080/14737175.2020.1713100. ; Löscher W, Potschka H, Sisodiya SM, Vezzani A (2020) Drug Resistance in epilepsy: clinical impact, potential mechanisms, and new innovative treatment options. Pharmacol Rev 72:606–638. https://doi.org/10.1124/pr.120.019539. (PMID: 10.1124/pr.120.019539325409597300324) ; Fang M, Xi Z-Q, Wu Y, Wang X-F (2011) A new hypothesis of drug refractory epilepsy: neural network hypothesis. 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(PMID: 10.1186/s13072-015-0011-y259777074430927) Grant Information: PI2017/02244 Instituto de Salud Carlos III; CAM.IND2017/BMD-7578 Comunidad de Madrid Contributed Indexing: Keywords: DNA methylation array; Drug-resistant epilepsy; Epigenetic; Epigenome-wide association study (EWAS); Epilepsy biomarkers Entry Date(s): Date Created: 20230105 Date Completed: 20230307 Latest Revision: 20230307 Update Code: 20231215

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