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Conserved DNA Methylation Signatures in Early Maternal Separation and in Twins Discordant for CO 2 Sensitivity.

Conserved DNA Methylation Signatures in Early Maternal Separation and in Twins Discordant for CO 2 Sensitivity.

Authors :
Giannese F
Luchetti A
Barbiera G
Lampis V
Zanettini C
Knudsen GP
Scaini S
Lazarevic D
Cittaro D
D'Amato FR
Battaglia M
Source :
Scientific reports [Sci Rep] 2018 Feb 02; Vol. 8 (1), pp. 2258. Date of Electronic Publication: 2018 Feb 02.
Publication Year :
2018

Abstract

Respiratory and emotional responses to blood-acidifying inhalation of CO <subscript>2</subscript> are markers of some human anxiety disorders, and can be enhanced by repeatedly cross-fostering (RCF) mouse pups from their biological mother to unrelated lactating females. Yet, these dynamics remain poorly understood. We show RCF-associated intergenerational transmission of CO <subscript>2</subscript> sensitivity in normally-reared mice descending from RCF-exposed females, and describe the accompanying alterations in brain DNA methylation patterns. These epigenetic signatures were compared to DNA methylation profiles of monozygotic twins discordant for emotional reactivity to a CO <subscript>2</subscript> challenge. Altered methylation was consistently associated with repeated elements and transcriptional regulatory regions among RCF-exposed animals, their normally-reared offspring, and humans with CO <subscript>2</subscript> hypersensitivity. In both species, regions bearing differential methylation were associated with neurodevelopment, circulation, and response to pH acidification processes, and notably included the ASIC2 gene. Our data show that CO <subscript>2</subscript> hypersensitivity is associated with specific methylation clusters and genes that subserve chemoreception and anxiety. The methylation status of genes implicated in acid-sensing functions can inform etiological and therapeutic research in this field.

Details

Language :
English
ISSN :
2045-2322
Volume :
8
Issue :
1
Database :
MEDLINE
Journal :
Scientific reports
Publication Type :
Academic Journal
Accession number :
29396481
Full Text :
https://doi.org/10.1038/s41598-018-20457-3