DNA methyltransferase isoforms expression in the temporal lobe of epilepsy patients with a history of febrile seizures
21 июля 2021 года
13:31
DNA methyltransferase isoforms expression in the temporal lobe of epilepsy patients with a history of febrile seizures
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Title: DNA methyltransferase isoforms expression in the temporal lobe of epilepsy patients with a history of febrile seizures
Author, co-author: de Nijs, Laurence; Choe, K.; Steinbusch, H.; Schijns, O. E. M. G.; Dings, J.; Van Den Hove, D. L. A.; Rutten, B. P. F.; Hoogland, G.
Abstract: Background: Temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) is a common pharmaco-resistant epilepsy referred for adult epilepsy surgery. Though associated with prolonged febrile seizures (FS) in childhood, the neurobiological basis for this relationship is not fully understood and currently no preventive or curative therapies are available. DNA methylation, an epigenetic mechanism catalyzed by DNA methyltransferases (DNMTs), potentially plays a pivotal role in epileptogenesis associated with FS. In an attempt to start exploring this notion, the present cross-sectional pilot study investigated whether global DNA methylation levels (5-mC and 5-hmC markers) and DNMT isoforms (DNMT1, DNMT3a1, and DNMT3a2) expression would be different in hippocampal and neocortical tissues between controls and TLE patients with or without a history of FS. Results: We found that global DNA methylation levels and DNMT3a2 isoform expression were lower in the hippocampus for all TLE groups when compared to control patients, with a more significant decrease amongst the TLE groups with a history of FS. Interestingly, we showed that DNMT3a1 expression was severely diminished in the hippocampus of TLE patients with a history of FS in comparison with control and other TLE groups. In the neocortex, we found a higher expression of DNMT1 and DNMT3a1 as well as increased levels of global DNA methylation for all TLE patients compared to controls. Conclusion: Together, the findings of this descriptive cross-sectional pilot study demonstrated brain region-specific changes in DNMT1 and DNMT3a isoform expression as well as global DNA methylation levels in human TLE with or without a history of FS. They highlighted a specific implication of DNMT3a isoforms in TLE after FS. Therefore, longitudinal studies that aim at targeting DNMT3a isoforms to evaluate the potential causal relationship between FS and TLE or treatment of FS-induced epileptogenesis seem warranted. © 2019 The Author(s).

Связанные объекты: #A (найти в новостях), #TLE (найти в новостях), #They (найти в новостях).

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Title :
DNA methyltransferase isoforms expression in the temporal lobe of epilepsy patients with a history of febrile seizures
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[School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Universiteitssingel 50, Maastricht, 6229, Netherlands, Department of Neurosurgery, Maastricht University Medical Center, Maastricht, Netherlands, Academic Center for Epileptology (ACE), Maastricht University Medical Center, Maastricht, Netherlands]
[School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Universiteitssingel 50, Maastricht, 6229, Netherlands, Department of Neurosurgery, Maastricht University Medical Center, Maastricht, Netherlands, Academic Center for Epileptology (ACE), Maastricht University Medical Center, Maastricht, Netherlands]
[School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Universiteitssingel 50, Maastricht, 6229, Netherlands, Department of Neurosurgery, Maastricht University Medical Center, Maastricht, Netherlands, Academic Center for Epileptology (ACE), Maastricht University Medical Center, Maastricht, Netherlands]
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Keywords :
[en] DNA methylation ; DNA methyltransferases ; Epigenetics ; Febrile seizures ; Temporal lobe epilepsy ; DNA (cytosine 5) methyltransferase 1 ; DNA methyltransferase ; DNA methyltransferase 3A ; DNA methyltransferase 3A1 ; DNA methyltransferase 3A2 ; DNA (cytosine 5) methyltransferase ; DNA (cytosine 5) methyltransferase 1 ; DNA methyltransferase 3A ; DNMT1 protein, human ; Article ; Case-Control Studies ; Cross-Sectional Studies ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases ; DNA Methylation ; Epigenesis, Genetic ; Epilepsy, Temporal Lobe ; Female ; Gene Expression Regulation, Neoplastic ; Hippocampus ; Humans ; Male ; Neocortex ; Organ Specificity ; Pilot Projects ; Seizures, Febrile
Abstract :
[en] Background: Temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) is a common pharmaco-resistant epilepsy referred for adult epilepsy surgery. Though associated with prolonged febrile seizures (FS) in childhood, the neurobiological basis for this relationship is not fully understood and currently no preventive or curative therapies are available. DNA methylation, an epigenetic mechanism catalyzed by DNA methyltransferases (DNMTs), potentially plays a pivotal role in epileptogenesis associated with FS. In an attempt to start exploring this notion, the present cross-sectional pilot study investigated whether global DNA methylation levels (5-mC and 5-hmC markers) and DNMT isoforms (DNMT1, DNMT3a1, and DNMT3a2) expression would be different in hippocampal and neocortical tissues between controls and TLE patients with or without a history of FS. Results: We found that global DNA methylation levels and DNMT3a2 isoform expression were lower in the hippocampus for all TLE groups when compared to control patients, with a more significant decrease amongst the TLE groups with a history of FS. Interestingly, we showed that DNMT3a1 expression was severely diminished in the hippocampus of TLE patients with a history of FS in comparison with control and other TLE groups. In the neocortex, we found a higher expression of DNMT1 and DNMT3a1 as well as increased levels of global DNA methylation for all TLE patients compared to controls. Conclusion: Together, the findings of this descriptive cross-sectional pilot study demonstrated brain region-specific changes in DNMT1 and DNMT3a isoform expression as well as global DNA methylation levels in human TLE with or without a history of FS. They highlighted a specific implication of DNMT3a isoforms in TLE after FS. Therefore, longitudinal studies that aim at targeting DNMT3a isoforms to evaluate the potential causal relationship between FS and TLE or treatment of FS-induced epileptogenesis seem warranted. © 2019 The Author(s).
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