title: Endoplasmic reticulum stress is involved in the colonic epithelium damage induced by maternal separation.
abstract: BACKGROUND
  Maternal separation (MS) leads to intestinal barrier dysfunction in neonatal mice. Endoplasmic reticulum (ER) stress is associated with apoptosis and pro-inflammatory response induction. We hypothesized that MS induced gut damage is associated with ER stress and that administration of an ER stress inhibitor protects gut damage.
  
  
  METHODS
  C57BL/6 mice received intraperitoneal PBS (n=10) or Salubrinal (1mg/kg/day, n=10). MS was performed soon after treatment for 3h daily between P5 and P9. Ten untreated neonatal mice served as control. The colon was harvested on P9 and analyzed for ER stress markers (BiP, CHOP), apoptosis (CC3), goblet cell number per crypt and crypt length (Alcian blue, hematoxylin/eosin), and transcellular permeability (Ussing chamber). Groups were compared using one-way ANOVA with Bonferroni post-test.
  
  
  RESULTS
  Compared to controls, MS mice had higher relative protein expression of ER stress and apoptosis markers (p<0.05) and reduced goblet cell number per crypt and crypt length (p<0.001). In comparison to PBS mice, Salubrinal treated mice had higher goblet cell number (p<0.05), crypt length (p<0.001), and lower transcellular permeability (p<0.05).
  
  
  CONCLUSIONS
  Maternal separation induces ER stress and causes colon damage, but ER stress inhibitor protects morphology and permeability. This provides insights on bowel pathogenesis and potential novel treatments for diseases such as necrotizing enterocolitis.
authors.affiliation: Division of General and Thoracic Surgery, Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Division of General and Thoracic Surgery, Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Augusto
authors.initials: A
authors.lastname: Zani
authors.affiliation: Division of General and Thoracic Surgery, Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Carol
authors.initials: C
authors.lastname: Lee
authors.affiliation: Division of General and Thoracic Surgery, Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Elke
authors.initials: E
authors.lastname: Zani-Ruttenstock
authors.affiliation: Division of General and Thoracic Surgery, Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Division of General and Thoracic Surgery, Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Xinpei
authors.initials: X
authors.lastname: Li
authors.affiliation: Division of General and Thoracic Surgery, Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Wan
authors.initials: W
authors.lastname: Ip
authors.affiliation: Department of Pediatrics and Gastroenterology, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Tanja
authors.initials: T
authors.lastname: Gonska
authors.affiliation: Division of General and Thoracic Surgery, Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address: agostino.pierro@sickkids.ca.
authors.forename: Agostino
authors.initials: A
authors.lastname: Pierro
mesh_terms: D000818:Animals; D017209:Apoptosis; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D002934:Cinnamates / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D005765:Gastrointestinal Agents / Q000494:pharmacology; D007410:Intestinal Diseases / Q000503:physiopathology* / Q000523:psychology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology*; D008426:Maternal Deprivation; D051379:Mice; D008810:Mice, Inbred C57BL; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D002934:Cinnamates; D005765:Gastrointestinal Agents; C496827:salubrinal; D013890:Thiourea
keywords: ER stress; Goblet cells; Intestine; NEC; Necrotizing enterocolitis; Ulcerative colitis