title: Buserelin treatment to rats causes enteric neurodegeneration with moderate effects on CRF-immunoreactive neurons and Enterobacteriaceae in colon, and in acetylcholine-mediated permeability in ileum.
abstract: BACKGROUND
  The gonadotropin-releasing hormone (GnRH) analog buserelin causes enteric neuronal loss. Acute stress or injection of corticotropin-releasing factor (CRF) affects motility, secretion, and barrier function of the gastrointestinal tract. The aim of the study was to characterize the CRF immunoreactivity in enteric neurons after buserelin treatment, and to evaluate possible effects of enteric neuropathy on gut microbiota, intestinal permeability, and stress response behavior.
  
  
  RESULTS
  Sixty rats were given buserelin (20 μg) or saline subcutaneously for 5 days, repeated four times with 3 weeks in-between. At the study end, enteric neuronal density, enteric expression of CRF, gut microbial composition, and plasma levels of adrenocorticotropic hormone (ACTH) and CRF were analyzed. Intestinal permeability was examined in Ussing chambers and the reaction to stressful events was measured by behavior tests. Buserelin treatment reduced the number of neurons along the entire gastrointestinal tract, with increased relative numbers of CRF-immunoreactive submucosal and myenteric neurons in colon (p < 0.05 and p < 0.01, respectively). The overall microbial diversity and relative abundance did not differ between groups, but Enterobacteriaceae was decreased in colon in buserelin-treated rats (p = 0.020). Basal intestinal permeability did not differ between groups, whereas carbachol stimulation increased ileum permeability in controls (p < 0.05), but not in buserelin-treated rats. Buserelin did not affect stress behavior.
  
  
  CONCLUSIONS
  Although buserelin treatment leads to enteric neuronal loss along the gastrointestinal tract with an increased percentage of CRF-immunoreactive neurons in colon, the physiology is well preserved, with modest effects on colon microbiota and absence of carbachol-induced permeability in ileum as the only observed changes.
authors.affiliation: Division of Internal Medicine, Department of Clinical Sciences, Skåne University Hospital, Lund University, Inga Marie Nilssons street 32, 205 02, Malmö, Sweden. elin@imagene-it.se.|Neurogastroenterology Unit, Department of Experimental Medical Science, BMC B11, Lund University, 221 84, Lund, Sweden. elin@imagene-it.se.
authors.forename: Elin
authors.initials: E
authors.lastname: Sand
authors.affiliation: Department of Food Technology, Engineering and Nutrition, Lund University, 22100, Lund, Sweden. caroline.linninge@food.lth.se.
authors.forename: Caroline
authors.initials: C
authors.lastname: Linninge
authors.affiliation: Department of Biology, Functional Biology, Lund University, 221 84, Lund, Sweden. liudmyla.lozinska@med.lu.se.
authors.forename: Liudmyla
authors.initials: L
authors.lastname: Lozinska
authors.affiliation: Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, 405 30, Gothenburg, Sweden. emil.egecioglu@neuro.gu.se.
authors.forename: Emil
authors.initials: E
authors.lastname: Egecioglu
authors.affiliation: Division of Internal Medicine, Department of Clinical Sciences, Skåne University Hospital, Lund University, Inga Marie Nilssons street 32, 205 02, Malmö, Sweden. bodil.roth@med.lu.se.
authors.forename: Bodil
authors.initials: B
authors.lastname: Roth
authors.affiliation: Department of Food Technology, Engineering and Nutrition, Lund University, 22100, Lund, Sweden. goran.molin@food.lth.se.
authors.forename: Göran
authors.initials: G
authors.lastname: Molin
authors.affiliation: Department of Biology, Functional Biology, Lund University, 221 84, Lund, Sweden. bjorn.westrom@biol.lu.se.
authors.forename: Björn
authors.initials: B
authors.lastname: Weström
authors.affiliation: Neurogastroenterology Unit, Department of Experimental Medical Science, BMC B11, Lund University, 221 84, Lund, Sweden. eva.ekblad@med.lu.se.
authors.forename: Eva
authors.initials: E
authors.lastname: Ekblad
authors.affiliation: Division of Internal Medicine, Department of Clinical Sciences, Skåne University Hospital, Lund University, Inga Marie Nilssons street 32, 205 02, Malmö, Sweden. bodil.ohlsson@med.lu.se.
authors.forename: Bodil
authors.initials: B
authors.lastname: Ohlsson
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002064:Buserelin / Q000009:adverse effects*; D003106:Colon / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D004755:Enterobacteriaceae / Q000187:drug effects; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000009:adverse effects / Q000031:analogs & derivatives*; D007082:Ileum / Q000187:drug effects; D007410:Intestinal Diseases / Q000139:chemically induced*; D009422:Nervous System Diseases / Q000139:chemically induced*; D009474:Neurons / Q000187:drug effects; D010539:Permeability; D051381:Rats
chemical_list: D007987:Gonadotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone; D000109:Acetylcholine; D002064:Buserelin