| Literature DB >> 30820471 |
Yasuhiko Yamamoto1, Mingkun Liang2, Seiichi Munesue3, Kisaburo Deguchi4, Ai Harashima3, Kazumi Furuhara2, Teruko Yuhi2, Jing Zhong2, Shirin Akther2, Hisanori Goto3, Yuya Eguchi3, Yasuko Kitao5, Osamu Hori5, Yoshitake Shiraishi6, Noriyuki Ozaki6, Yu Shimizu3,7, Tomoya Kamide5,7, Akifumi Yoshikawa5,7, Yasuhiko Hayashi7, Mitsutoshi Nakada7, Olga Lopatina2,8, Maria Gerasimenko2, Yulia Komleva8, Natalia Malinovskaya8, Alla B Salmina2,8, Masahide Asano9, Katsuhiko Nishimori10, Steven E Shoelson11, Hiroshi Yamamoto3,12, Haruhiro Higashida13,14.
Abstract
Oxytocin sets the stage for childbirth by initiating uterine contractions, lactation and maternal bonding behaviours. Mice lacking secreted oxcytocin (Oxt -/-, Cd38 -/-) or its receptor (Oxtr -/-) fail to nurture. Normal maternal behaviour is restored by peripheral oxcytocin replacement in Oxt -/- and Cd38 -/-, but not Oxtr -/- mice, implying that circulating oxcytocin crosses the blood-brain barrier. Exogenous oxcytocin also has behavioural effects in humans. However, circulating polypeptides are typically excluded from the brain. We show that oxcytocin is transported into the brain by receptor for advanced glycation end-products (RAGE) on brain capillary endothelial cells. The increases in oxcytocin in the brain which follow exogenous administration are lost in Ager -/- male mice lacking RAGE, and behaviours characteristic to abnormalities in oxcytocin signalling are recapitulated in Ager -/- mice, including deficits in maternal bonding and hyperactivity. Our findings show that RAGE-mediated transport is critical to the behavioural actions of oxcytocin associated with parenting and social bonding.Entities:
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Year: 2019 PMID： 30820471 PMCID： PMC6389896 DOI： 10.1038/s42003-019-0325-6
Source DB: PubMed Journal: Commun Biol ISSN： 2399-3642