title: Structural and functional consequences of buserelin-induced enteric neuropathy in rat.
abstract: BACKGROUND
  Women treated with gonadotropin-releasing hormone (GnRH) analogs may develop enteric neuropathy and dysmotility. Administration of a GnRH analog to rats leads to similar degenerative neuropathy and ganglioneuritis. The aim of this study on rat was to evaluate the early GnRH-induced enteric neuropathy in terms of distribution of neuronal subpopulations and gastrointestinal (GI) function.
  
  
  METHODS
  Forty rats were given the GnRH analog buserelin (20 μg, 1 mg/ml) or saline subcutaneously, once daily for 5 days, followed by 3 weeks of recovery, representing one treatment session. Two weeks after the fourth treatment session, the animals were tested for GI transit time and galactose absorption, and fecal weight and fat content was analyzed. After sacrifice, enteric neuronal subpopulations were analyzed. Blood samples were analyzed for zonulin and antibodies against GnRH and luteinizing hormone, and their receptors.
  
  
  RESULTS
  Buserelin treatment transiently increased the body weight after 5 and 9 weeks (p < 0.001). Increased estradiol in plasma and thickened uterine muscle layers indicate high estrogen activity. The numbers of both submucous and myenteric neurons were reduced by 27%-61% in ileum and colon. The relative numbers of neurons containing calcitonin gene-related peptide (CGRP), cocaine- and amphetamine-related transcript (CART), galanin, gastrin-releasing peptide (GRP), neuropeptide Y (NPY), nitric oxide synthase (NOS), serotonin, substance P (SP), vasoactive intestinal peptide (VIP) or vesicular acetylcholine transporter (VAchT), and their nerve fiber density, were unchanged after buserelin treatment, but the relative number of submucous neurons containing somatostatin tended to be increased (p = 0.062). The feces weight decreased in buserelin-treated rats (p < 0.01), whereas feces fat content increased (p < 0.05), compared to control rats. Total GI transit time, galactose absorption, zonulin levels in plasma, and antibody titers in serum were unaffected by buserelin treatment.
  
  
  CONCLUSIONS
  A marked enteric neuronal loss with modest effects on GI function is found after buserelin treatment. Increased feces fat content is suggested an early sign of dysfunction.
authors.affiliation: Department of Clinical Sciences, Division of Internal Medicine Skåne University Hospital, Lund University, Inga Marie Nilssons street 32, S-205 02, Malmö, Sweden. elin.sand@med.lu.se.|Department of Experimental Medical Science, Neurogastroenterology Unit, BMC B11, Lund University, 221 84, Lund, Sweden. elin.sand@med.lu.se.
authors.forename: Elin
authors.initials: E
authors.lastname: Sand
authors.affiliation: Department of Clinical Sciences, Division of Internal Medicine Skåne University Hospital, Lund University, Inga Marie Nilssons street 32, S-205 02, Malmö, Sweden. bodil.roth@med.lu.se.
authors.forename: Bodil
authors.initials: B
authors.lastname: Roth
authors.affiliation: Department of Biology, Functional Biology, Lund University, 221 00, Lund, Sweden. bjorn.westrom@biol.lu.se.
authors.forename: Björn
authors.initials: B
authors.lastname: Weström
authors.affiliation: Department of Medicinal Chemistry, CVMD, AstraZeneca, Mölndal, Sweden. peter.g.bonn@gmail.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Bonn
authors.affiliation: Department of Experimental Medical Science, Neurogastroenterology Unit, BMC B11, Lund University, 221 84, Lund, Sweden. eva.ekblad@med.lu.se.
authors.forename: Eva
authors.initials: E
authors.lastname: Ekblad
authors.affiliation: Department of Clinical Sciences, Division of Internal Medicine Skåne University Hospital, Lund University, Inga Marie Nilssons street 32, S-205 02, Malmö, Sweden. bodil.ohlsson@med.lu.se.
authors.forename: Bodil
authors.initials: B
authors.lastname: Ohlsson
mesh_terms: D000818:Animals; D002064:Buserelin; D003106:Colon / Q000473:pathology; D004195:Disease Models, Animal; D004958:Estradiol / Q000097:blood; D005243:Feces / Q000737:chemistry; D005260:Female; D041981:Gastrointestinal Tract / Q000503:physiopathology*; D005772:Gastrointestinal Transit; D007082:Ileum / Q000473:pathology; D007418:Intestinal Pseudo-Obstruction / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D008055:Lipids / Q000032:analysis; D009474:Neurons / Q000737:chemistry / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000473:pathology; D014599:Uterus / Q000033:anatomy & histology
chemical_list: D008055:Lipids; D004958:Estradiol; D002064:Buserelin