Histone Modifications in a Mouse Model of Early Adversities and Panic Disorder: Role for Asic1 and Neurodevelopmental Genes.

摘要: Hyperventilation following transient, CO2-induced acidosis is ubiquitous in mammals and heritable. In humans, respiratory emotional hypersensitivity to CO2 marks separation anxiety panic disorders, enhanced by early-life adversities. Mice exposed the repeated cross-fostering paradigm (RCF) of interference with maternal environment show heightened hyperventilation 6% CO2-enriched air. Gene-environment interactions affect both humans mice. We therefore hypothesised that epigenetic modifications increased expression genes involved pH-detection could explain these relationships. Medullae oblongata RCF- normally-reared female outbred mice were assessed ChIP-seq for H3Ac, H3K4me3, H3K27me3 histone modifications, SAGE differential gene expression. Integration multiple experiments network analysis revealed an active component 148 pointing mTOR signalling pathway nociception. Among genes, Asic1 showed mRNA expression, coherent RCF-mice's altered Functional enrichment transcript analyses yielded a consistent picture enhancement several affecting chemoception, neurodevelopment, emotionality. Particularly, results support recent human findings responses, provide new perspectives on how early adversities interplay key components related disorders.