title: Myenteric plexus injury and apoptosis in experimental colitis.
abstract: Intestinal inflammatory conditions are associated with structural and functional alterations of the enteric nervous system (ENS). While injury to the enteric nervous system is well described, the mechanisms of neuronal injury and neuronal cell loss remain unclear. The aim of the present study was to examine the neural consequences of distal colitis and to assess the role of neutrophil granulocytes in mediating these changes. Colitis was induced in C3H/HEN female mice with dinitrobenzene sulfonic acid. The mice were then sacrificed at 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, 120 h post instillation of dinitrobenzene sulfonic acid. The inflammatory response was assessed by macroscopic damage score, myeloperoxidase activity and histology. HuC/D and PGP 9.5 immunostaining was used to examine myenteric plexus density and structure, neural cell body numbers and distribution in cross-section and whole mount preparations. Apoptosis was investigated in whole mount preparations double stained with HuC/D and activated caspase-3 or cleaved poly (ADP-ribose) polymerase (PARP). Dinitrobenzene sulfonic acid-induced colitis was associated with a rapid and significant loss of HuC/D immunoreactive myenteric plexus neuronal cell bodies (42% decrease relative to control) that remained unchanged between 6 and 120 h. No change in myenteric plexus density was observed with PGP 9.5 immunostaining. Neuronal apoptosis was evident between 0.5 and 3 h. PARP immunoreactive neurons ranged between 1% and 2.5%. Colitis was associated with significant impairment in colonic propulsive function. Pre-treatment of mice with anti-neutrophil serum attenuated the inflammatory response and partially reduced the extent of myenteric plexus neuronal cell loss. Taken together, these data suggest that acute colitis is associated with loss of myenteric plexus neurons that is partly mediated by neutrophil granulocyte infiltration and is accompanied by impairment of colonic motility.
authors.affiliation: British Columbia Research Institute, Vancouver, British Columbia, Canada V6H 3V4.
authors.forename: Lee
authors.initials: L
authors.lastname: Boyer
authors.forename: Mehran
authors.initials: M
authors.lastname: Ghoreishi
authors.forename: Valerie
authors.initials: V
authors.lastname: Templeman
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Vallance
authors.forename: Alison M
authors.initials: AM
authors.lastname: Buchan
authors.forename: Gareth
authors.initials: G
authors.lastname: Jevon
authors.forename: Kevan
authors.initials: K
authors.lastname: Jacobson
mesh_terms: D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000627:therapeutic use; D017209:Apoptosis; D001557:Benzenesulfonates; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D051959:ELAV Proteins; D000067778:ELAV-Like Protein 3; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009197:Myenteric Plexus / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D018709:Statistics, Nonparametric; D013997:Time Factors; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001557:Benzenesulfonates; D051959:ELAV Proteins; D000067778:ELAV-Like Protein 3; C490263:Elavl3 protein, mouse; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C007488:dinitrobenzenesulfonic acid; D009195:Peroxidase; D043222:Ubiquitin Thiolesterase; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases