Open AccessA Methyltransferase Inhibitor (Decitabine) Alleviates Intergenerational Effects of Paternal Neonatal Exposure to Anesthesia With Sevoflurane
Author(s) -
Ning Xu,
Lei Lei,
Yung-Yang Lin,
Ling-Sha Ju,
Timothy E. Morey,
Nikolaus Gravenstein,
Jianjun Yang,
Anatoly E. Martynyuk
Publication year - 2020
Publication title -
anesthesia and analgesia/anesthesia and analgesia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.404
H-Index - 201
eISSN - 1526-7598
pISSN - 0003-2999
DOI - 10.1213/ane.0000000000005097
Subject(s) - sevoflurane , prepulse inhibition , offspring , medicine , corticosterone , endocrinology , decitabine , methyltransferase , anesthesia , biology , methylation , gene expression , dna methylation , hormone , pregnancy , gene , genetics , psychiatry , schizophrenia (object oriented programming)
Neonatal exposure to sevoflurane induces neurobehavioral and neuroendocrine abnormalities in exposed male rats (generation F0) and neurobehavioral, but not neuroendocrine, abnormalities in their male, but not female, offspring (generation F1). These effects of sevoflurane are accompanied by a hypermethylated neuron-specific K-2Cl (Kcc2) Cl exporter gene in the F0 spermatozoa and the F1 male hypothalamus, while the gene's expression is reduced in the F0 and F1 hypothalamus. We investigated whether inhibition of deoxyribonucleic acid methyltransferases (DNMTs) before paternal sevoflurane exposure could alleviate the anesthetic's F0 and F1 effects.