DNA methyltransferase isoforms expression in the temporal lobe of epilepsy patients with a history of febrile seizures

• DOI: 10.1186/s13148-019-0721-2
• Publication Date: 2019-08-19T13:02:39Z
• Authors: Laurence de Nijs; Kyonghwan Choe; Hellen Steinbusch; Olaf E. M. G. Sch...; Jim Dings; Daniel L. A. van ...; Bart P. F. Rutten; Govert Hoogland
• Keywords: DNMT1; Hippocampal sclerosis; DNA methyltransferase; Neocortex

Temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) is a common pharmaco-resistant referred for adult surgery. Though associated prolonged febrile seizures (FS) in childhood, the neurobiological basis this relationship not fully understood and currently no preventive or curative therapies are available. DNA methylation, an epigenetic mechanism catalyzed by methyltransferases (DNMTs), potentially plays pivotal role epileptogenesis FS. In attempt to start exploring notion, present cross-sectional pilot study investigated whether global methylation levels (5-mC 5-hmC markers) DNMT isoforms (DNMT1, DNMT3a1, DNMT3a2) expression would be different neocortical tissues between controls TLE patients without history of We found that DNMT3a2 isoform were lower hippocampus all groups when compared control patients, more significant decrease amongst Interestingly, we showed DNMT3a1 was severely diminished FS comparison other groups. neocortex, higher DNMT1 as well increased controls. Together, findings descriptive demonstrated brain region-specific changes DNMT3a human They highlighted specific implication after Therefore, longitudinal studies aim at targeting evaluate potential causal treatment FS-induced seem warranted.