title: Colostrum oxytocin modulates cellular stress response, inflammation, and autophagy markers in newborn rat gut villi.
abstract: Little is known about the role of oxytocin (OT) in colostrum during early gut colonization. We previously showed that transient OT receptor (OTR) expression on newborn rat enterocytes coincides with the milk-suckling period, and that OT activates endoplasmic reticulum stress sensors in cultured enterocytes. Here, we explored whether colostrum-OT attenuates stress in newborn villi primed and unprimed by colostrum by measuring levels of stress markers including BiP (an ER chaperone), eIF2a (translation initiation factor), and pPKR (eIF2a kinase). We also measured two inflammation-signaling proteins NF-κB and its inhibitor IκB. To test the impact of colostrum on autophagy, we measured a marker of autophagy initiation, LC3A. Colostrum increased inactive p-eIF2a, p-PKR and IκB and reduced p-IκB, BiP and LC3A. LPS increased and OT decreased p-IkB. BiP (GRP78) was higher in unprimed than primed villi. Together, these data suggest that colostrum OT attenuates the impact of inflammation on postnatal gut villi and that OT enhances autophagy to protect against amino acid insufficiency-induced stress during the interval between birth and the first feeding.
authors.affiliation: Department of Psychiatry, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: bk2348@cumc.columbia.edu.
authors.forename: Benjamin Y
authors.initials: BY
authors.lastname: Klein
authors.affiliation: Department of Psychiatry, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology & Cell Biology, Columbia University Medical Center, New York, NY 10032, USA; Department of Psychiatry, Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Hadassah
authors.initials: H
authors.lastname: Tamir
authors.affiliation: Department of Psychiatry, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ludwig
authors.affiliation: EB Sciences, Oakland, CA 94611, USA.
authors.forename: Sara B
authors.initials: SB
authors.lastname: Glickstein
authors.affiliation: Department of Psychiatry, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology & Cell Biology, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: mgw13@columbia.edu.
authors.forename: Martha G
authors.initials: MG
authors.lastname: Welch
authors.forename: M
authors.initials: M
authors.lastname: Anwar
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001343:Autophagy / Q000187:drug effects / Q000276:immunology; D003126:Colostrum / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006360:Heat-Shock Proteins / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008871:Microvilli / Q000187:drug effects; D010121:Oxytocin / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D006360:Heat-Shock Proteins; D018836:Inflammation Mediators; D010121:Oxytocin; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP
keywords: Enterocytes; GRP94; IκB; LC3A; Stress response; eIF2a