title: Effects of prenatal Poly I:C exposure on global histone deacetylase (HDAC) and DNA methyltransferase (DNMT) activity in the mouse brain.
abstract: The aim of our study was to investigate the brain-specific epigenetic effects on global enzymatic histone deacetylase (HDAC) and DNA methyltransferase (DNMT) activity after prenatal exposure to maternal immune challenge by polyinosinic:polycytidylic acid (Poly I:C) at gestational day (GD) 17 in C57BL/6JRccHsd mouse offspring. Pregnant mice were randomly divided into 2 groups, receiving either 5 mg/kg Poly I:C or phosphate buffered saline (PBS) intravenously at GD 17. Subsequently, the effects on whole brain enzymatic HDAC and DNMT activity and the protein levels of various HDAC isoforms were assessed in the offspring. Overall, a significant sex × treatment interaction effect was observed after prenatal exposure to maternal immune challenge by Poly I:C, indicative of increased global HDAC activity particularly in female offspring from mothers injected with Poly I:C when compared to controls. Results on the levels of specific HDAC isoforms suggested that neither differences in the levels of HDAC1, HDAC2, HDAC3, HDAC4 or HDAC6 could explain the increased global HDAC activity observed in female Poly I:C offspring. In conclusion, we show that Poly I:C administration to pregnant mice alters global brain HDAC, but not DNMT activity in adult offspring, whereas it is still unclear which specific HDAC(s) mediate(s) this effect. These results indicate the necessity for further research on the epigenetic effects of Poly I:C.
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre+, Universiteitssingel 50, Room 1.148, 6229 ER, Maastricht, The Netherlands. yarapujol@gmail.com.
authors.forename: Yara
authors.initials: Y
authors.lastname: Pujol Lopez
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre+, Universiteitssingel 50, Room 1.148, 6229 ER, Maastricht, The Netherlands.
authors.forename: Gunter
authors.initials: G
authors.lastname: Kenis
authors.affiliation: Psychiatric Hospital, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Waldtraud
authors.initials: W
authors.lastname: Stettinger
authors.affiliation: Psychiatric Hospital, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Neumeier
authors.affiliation: Psychiatric Hospital, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: de Jonge
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre+, Universiteitssingel 50, Room 1.148, 6229 ER, Maastricht, The Netherlands.
authors.forename: Harry W M
authors.initials: HW
authors.lastname: Steinbusch
authors.affiliation: Psychiatric Hospital, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Zill
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre+, Universiteitssingel 50, Room 1.148, 6229 ER, Maastricht, The Netherlands.|Laboratory of Translational Neuroscience, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Daniel L A
authors.initials: DL
authors.lastname: van den Hove
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre+, Universiteitssingel 50, Room 1.148, 6229 ER, Maastricht, The Netherlands.|Psychiatric Hospital, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Aye M
authors.initials: AM
authors.lastname: Myint
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000201:enzymology / Q000276:immunology*
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D006655:Histone Deacetylases; D011070:Poly I-C
keywords: Epigenetics; HDAC; Infection; Mouse; Poly I:C; Pregnancy