Conserved DNA Methylation Signatures in Early Maternal Separation and in Twins Discordant for CO2Sensitivity

F Giannese, Alessandra Luchetti, G Barbiera, V Lampis, C Zanettini, GP Knudsen, S Scaini, D Lazarevic, D Cittaro, FR D'Amato, M Battaglia

Research output: Contribution to journalArticle

Abstract

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).
Original languageEnglish
Article number2258
JournalScientific Reports
Volume8
Issue number5
DOIs
Publication statusPublished - 2018

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DNA Methylation
Carbon Monoxide
Foster Home Care
Methylation
Mothers
Hypersensitivity
Therapeutic Human Experimentation
Monozygotic Twins
Nucleic Acid Regulatory Sequences
Multigene Family
Anxiety Disorders
Epigenomics
Inhalation
Genes
Anxiety
Acids
Brain

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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 journalArticle

Giannese, F ; Luchetti, Alessandra ; Barbiera, G ; Lampis, V ; Zanettini, C ; Knudsen, GP ; Scaini, S ; Lazarevic, D ; Cittaro, D ; D'Amato, FR ; Battaglia, M. / Conserved DNA Methylation Signatures in Early Maternal Separation and in Twins Discordant for CO2Sensitivity. In: Scientific Reports. 2018 ; Vol. 8, No. 5.
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AU - Giannese, F

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AU - Lampis, V

AU - Zanettini, C

AU - Knudsen, GP

AU - Scaini, S

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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).

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