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

Respiratory and emotional responses to blood-acidifying inhalation of CO 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...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2018-02, Vol.8 (1), p.2258
Main Authors: Giannese, Francesca, Luchetti, Alessandra, Barbiera, Giulia, Lampis, Valentina, Zanettini, Claudio, Knudsen, Gun Peggy, Scaini, Simona, Lazarevic, Dejan, Cittaro, Davide, D'Amato, Francesca R, Battaglia, Marco
Format: Article
Language:English
Subjects:
Animals
Brain - drug effects
Brain - pathology
Carbon Dioxide - metabolism
DNA Methylation
Epigenesis, Genetic
Humans
Hydrogen-Ion Concentration
Mice
Twins, Monozygotic
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Respiratory and emotional responses to blood-acidifying inhalation of CO 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 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 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 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 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.
ISSN:2045-2322