Histone Modifications in a Mouse Model of Early Adversities and Panic Disorder: Role for Asic1 and Neurodevelopmental Genes
| Autor: | Roberto Coccurello, Francesca R. D’ Amato, Davide Cittaro, Alessandra Luchetti, Anna Moles, Armando Felsani, Valentina Lampis, Alessandro Guffanti, Elia Stupka, Marco Battaglia |
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| Přispěvatelé: | Cittaro, D, Lampis, V, Luchetti, A, Coccurello, R, Guffanti, A, Felsani, A, Moles, A, Stupka, E, D’Amato, F, Battaglia, MARCO MARIA |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Chromatin Immunoprecipitation medicine.medical_specialty Biology Article neurodevelopmental genes Mice 03 medical and health sciences 0302 clinical medicine Anxiety Separation medicine Animals Histone code RNA Messenger Epigenetics Psychiatry Regulation of gene expression Medulla Oblongata Multidisciplinary Asic1 histone modifications Behavioral neuroscience Gene Expression Profiling TOR Serine-Threonine Kinases Panic disorder Panic Sequence Analysis DNA medicine.disease Acid Sensing Ion Channels Histone Code Gene expression profiling Disease Models Animal 030104 developmental biology Gene Expression Regulation Panic Disorder H3K4me3 Anxiety Female Gene-Environment Interaction medicine.symptom Neuroscience 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Scientific Reports Scientific reports (Nature Publishing Group) 6 (2016). doi:10.1038/srep25131 info:cnr-pdr/source/autori:Cittaro D.; Lampis V.; Luchetti A.; Coccurello R.; Guffanti A.; Felsani A.; Moles A.; Stupka E.; D'Amato F.R.; Battaglia M./titolo:Histone modifications in a mouse model of early adversities and panic disorder: Role for Asic1 and neurodevelopmental genes/doi:10.1038%2Fsrep25131/rivista:Scientific reports (Nature Publishing Group)/anno:2016/pagina_da:/pagina_a:/intervallo_pagine:/volume:6 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep25131 |
| Popis: | Hyperventilation following transient, CO2-induced acidosis is ubiquitous in mammals and heritable. In humans, respiratory and emotional hypersensitivity to CO2 marks separation anxiety and panic disorders and is enhanced by early-life adversities. Mice exposed to the repeated cross-fostering paradigm (RCF) of interference with maternal environment show heightened separation anxiety and hyperventilation to 6% CO2-enriched air. Gene-environment interactions affect CO2 hypersensitivity in both humans and mice. We therefore hypothesised that epigenetic modifications and increased expression of genes involved in pH-detection could explain these relationships. Medullae oblongata of RCF- and normally-reared female outbred mice were assessed by ChIP-seq for H3Ac, H3K4me3, H3K27me3 histone modifications and by SAGE for differential gene expression. Integration of multiple experiments by network analysis revealed an active component of 148 genes pointing to the mTOR signalling pathway and nociception. Among these genes, Asic1 showed heightened mRNA expression, coherent with RCF-mice’s respiratory hypersensitivity to CO2 and altered nociception. Functional enrichment and mRNA transcript analyses yielded a consistent picture of enhancement for several genes affecting chemoception, neurodevelopment and emotionality. Particularly, results with Asic1 support recent human findings with panic and CO2 responses and provide new perspectives on how early adversities and genes interplay to affect key components of panic and related disorders. |
| Databáze: | OpenAIRE |
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