title: Epigenetics and cortical spreading depression: changes of DNA methylation level at retrotransposon sequences.
abstract: Cortical spreading depression (CSD) is an evolutionarily conserved phenomenon that involves a slow and self-propagating depolarization wave associated with spontaneous depression of electrical neuronal activity. CSD plays a central role in the pathophysiology of several brain diseases and is considered to be able to promote "Preconditioning". This phenomenon consists of the brain protecting itself against future injury by adaptation. Understanding of the molecular mechanisms underlying Preconditioning has significant clinical implications. We have already proposed that the long-lasting effects of CSD could be related to silencing of retrotransposon sequences by histone methylation. We analyzed DNA methylation of two retrotransposon sequences, LINE1 and L1, and their corresponding expression pattern after CSD induction. Based on immunoprecipitation assay of the methylated DNA (meDIP), we demonstrated hypermethylation of both sequences in preconditioned rat brain cortex compared with a control 24 h after CSD induction. Using quantitative PCR, we also showed that CSD induction caused a decrease of the transcript level of both retrotransposon sequences. Our data are consistent with the hypothesis of epigenetic modifications in Preconditioning-dependent neuroprotection by increasing genome stability via the silencing of retrotransposon sequences.
authors.affiliation: Department of Biology, University of Naples Federico II, via Cinthia, 80126, Naples, Italy.
authors.forename: Denise
authors.initials: D
authors.lastname: Drongitis
authors.affiliation: Department of Biology, University of Naples Federico II, via Cinthia, 80126, Naples, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Rainone
authors.affiliation: Department of Biology, University of Naples Federico II, via Cinthia, 80126, Naples, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Piscopo
authors.affiliation: Department of Experimental Medicine - Section of Human Physiology, Second University of Naples, Via De Crecchio 8, 80138, Naples, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Viggiano
authors.affiliation: Department of Experimental Medicine - Section of Human Physiology, Second University of Naples, Via De Crecchio 8, 80138, Naples, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Viggiano
authors.affiliation: Department of Experimental Medicine - Section of Human Physiology, Second University of Naples, Via De Crecchio 8, 80138, Naples, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: De Luca
authors.affiliation: Department of Biology, University of Naples Federico II, via Cinthia, 80126, Naples, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Fucci
authors.affiliation: Department of Biology, University of Naples Federico II, via Cinthia, 80126, Naples, Italy. aldo.donizetti@unina.it.
authors.forename: Aldo
authors.initials: A
authors.lastname: Donizetti
mesh_terms: D000818:Animals; D013181:Cortical Spreading Depression; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D065840:Protective Factors; D017208:Rats, Wistar
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat
keywords: Cortical spreading depression; DNA methylation; Neuroprotection; Neuroprotective genes; Preconditioning; Retrotransposon sequences