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Structural and functional consequences of buserelin-induced enteric neuropathy in rat

Sand, Elin LU ; Roth, Bodil LU ; Weström, Björn LU ; Bonn, Peter; Ekblad, Eva LU and Ohlsson, Bodil LU (2014) In BMC Gastroenterology 14.
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 mu g, 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... (More)
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 mu g, 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. (Less)
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organization
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Contribution to journal
publication status
published
subject
keywords
Enteric neuropathy, Enteric subpopulations, Gastrointestinal (GI) tract, Gonadotropin-releasing hormone (GnRH), Luteinizing hormone (LH), Somatostatin
in
BMC Gastroenterology
volume
14
publisher
BMC Biomedical Centre, Lund University
external identifiers
  • wos:000346744300001
  • scopus:84925395903
ISSN
1471-230X
DOI
10.1186/s12876-014-0209-7
language
English
LU publication?
yes
id
f1d0ecf3-3fc1-49d4-93d7-7ee7e5deefda (old id 4941673)
date added to LUP
2015-02-03 07:06:44
date last changed
2017-07-02 03:53:26
@article{f1d0ecf3-3fc1-49d4-93d7-7ee7e5deefda,
  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 mu g, 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 &lt; 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 &lt; 0.01), whereas feces fat content increased (p &lt; 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.},
  articleno    = {209},
  author       = {Sand, Elin and Roth, Bodil and Weström, Björn and Bonn, Peter and Ekblad, Eva and Ohlsson, Bodil},
  issn         = {1471-230X},
  keyword      = {Enteric neuropathy,Enteric subpopulations,Gastrointestinal (GI) tract,Gonadotropin-releasing hormone (GnRH),Luteinizing hormone (LH),Somatostatin},
  language     = {eng},
  publisher    = {BMC Biomedical Centre, Lund University},
  series       = {BMC Gastroenterology},
  title        = {Structural and functional consequences of buserelin-induced enteric neuropathy in rat},
  url          = {http://dx.doi.org/10.1186/s12876-014-0209-7},
  volume       = {14},
  year         = {2014},
}