Tong, Sok‐KengSok‐KengTongChang, Chun‐YungChun‐YungChangShih, Shang‐WuShang‐WuShihChua, Fang ZhiFang ZhiChuaHwang, Pung‐PungPung‐PungHwangMING-YI CHOU2025-06-092025-06-092025-04-25https://www.scopus.com/record/display.uri?eid=2-s2.0-105004080298&origin=resultslisthttps://scholars.lib.ntu.edu.tw/handle/123456789/729945Environmental temperatures substantially affect both endothermic and ectothermic vertebrates despite the two types of vertebrates having different adaptive strategies. Notably, the cellular and physiological mechanisms employed by ectothermic animals to cope with environmental changes remain poorly understood. Using zebrafish as a model, we investigated the detailed processes of cold acclimation in such fish. We analyzed the activation of oxytocin (OT) neurons and the release of peptide hormones into circulation within 3 h of cold exposure at 18°C, with this process followed by a dynamic downregulation at 24 h. Prolonged cold stress for 7 days resulted in a sustained reduction of plasma OT levels but a 30% increase in OT neuron numbers, which replenished the OT reservoir. We observed significant upregulation of RNA levels for proton ATPase (atp6v1aa) and epithelial calcium channel (trpv6) in the gills, indicating osmolarity acclimation by 7 days of cold exposure. Proton efflux was rapidly decreased within minutes of acute cold stress, but this reduction was mitigated by pretreatment with an OT agonist. Furthermore, OT was essential for the adaptive upregulation of ion-regulating genes (atp6v1aa and trpv6) during 7 days of cold acclimation. Although fundamental differences exist between endothermic and ectothermic animals, OT plays an evolutionarily conserved and pivotal role in cold acclimation, ensuring proper physiological adaptation to support survival under cold stress.en[SDGs]SDG3journal article10.1096/fj.202500161R