{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["9(40)"],"submitter":["Battaglia M"],"pubmed_abstract":["Early-life adversities are associated with altered defensive responses. Here, we demonstrate that the repeated cross-fostering (RCF) paradigm of early maternal separation is associated with enhancements of distinct homeostatic reactions: hyperventilation in response to hypercapnia and nociceptive sensitivity, among the first generation of RCF-exposed animals, as well as among two successive generations of their normally reared offspring, through matrilineal transmission. Parallel enhancements of acid-sensing ion channel 1 (ASIC1), ASIC2, and ASIC3 messenger RNA transcripts were detected transgenerationally in central neurons, in the medulla oblongata, and in periaqueductal gray matter of RCF-lineage animals. A single, nebulized dose of the ASIC-antagonist amiloride renormalized respiratory and nociceptive responsiveness across the entire RCF lineage. These findings reveal how, following an early-life adversity, a biological memory reducible to a molecular sensor unfolds, shaping adaptation mechanisms over three generations. Our findings are entwined with multiple correlates of human anxiety and pain conditions and suggest nebulized amiloride as a therapeutic avenue."],"journal":["Science advances"],"pagination":["eadi8750"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10550232"],"repository":["biostudies-literature"],"pubmed_title":["Enhanced harm detection following maternal separation: Transgenerational transmission and reversibility by inhaled amiloride."],"pmcid":["PMC10550232"],"pubmed_authors":["Godin AG","D'Amato FR","Lorenzo LE","Battaglia M","Rossignol O","Deguire J","De Koninck Y"],"additional_accession":[]},"is_claimable":false,"name":"Enhanced harm detection following maternal separation: Transgenerational transmission and reversibility by inhaled amiloride.","description":"Early-life adversities are associated with altered defensive responses. Here, we demonstrate that the repeated cross-fostering (RCF) paradigm of early maternal separation is associated with enhancements of distinct homeostatic reactions: hyperventilation in response to hypercapnia and nociceptive sensitivity, among the first generation of RCF-exposed animals, as well as among two successive generations of their normally reared offspring, through matrilineal transmission. Parallel enhancements of acid-sensing ion channel 1 (ASIC1), ASIC2, and ASIC3 messenger RNA transcripts were detected transgenerationally in central neurons, in the medulla oblongata, and in periaqueductal gray matter of RCF-lineage animals. A single, nebulized dose of the ASIC-antagonist amiloride renormalized respiratory and nociceptive responsiveness across the entire RCF lineage. These findings reveal how, following an early-life adversity, a biological memory reducible to a molecular sensor unfolds, shaping adaptation mechanisms over three generations. Our findings are entwined with multiple correlates of human anxiety and pain conditions and suggest nebulized amiloride as a therapeutic avenue.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Oct","modification":"2025-04-18T13:25:13.475Z","creation":"2025-04-04T08:46:14.477Z"},"accession":"S-EPMC10550232","cross_references":{"pubmed":["37792939"],"doi":["10.1126/sciadv.adi8750"]}}