Abstract
| Original language | English |
|---|---|
| Article number | 2258 |
| Journal | Scientific Reports |
| Volume | 8 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2018 |
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Conserved DNA Methylation Signatures in Early Maternal Separation and in Twins Discordant for CO2Sensitivity. / Giannese, F; Luchetti, Alessandra; Barbiera, G; Lampis, V; Zanettini, C; Knudsen, GP; Scaini, S; Lazarevic, D; Cittaro, D; D'Amato, FR; Battaglia, M.
In: Scientific Reports, Vol. 8, No. 5, 2258, 2018.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Conserved DNA Methylation Signatures in Early Maternal Separation and in Twins Discordant for CO2Sensitivity
AU - Giannese, F
AU - Luchetti, Alessandra
AU - Barbiera, G
AU - Lampis, V
AU - Zanettini, C
AU - Knudsen, GP
AU - Scaini, S
AU - Lazarevic, D
AU - Cittaro, D
AU - D'Amato, FR
AU - Battaglia, M
PY - 2018
Y1 - 2018
N2 - Respiratory and emotional responses to blood-acidifying inhalation of CO 2 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 2 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 2 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 2 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 2 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. © 2018 The Author(s).
AB - Respiratory and emotional responses to blood-acidifying inhalation of CO 2 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 2 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 2 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 2 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 2 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. © 2018 The Author(s).
U2 - 10.1038/s41598-018-20457-3
DO - 10.1038/s41598-018-20457-3
M3 - Article
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 5
M1 - 2258
ER -