Differential effects of experimental ulcerative colitis on P2X7 receptor expression in enteric neurons

Abstract

The digestive tracts of ulcerative colitis and Crohn's disease patients present with pathophysiological processes and intestinal necrosis. This study examined the P2X7 receptor and changes in the distal colon in enteric neurons of rats with experimental ulcerative colitis. The analysis was performed in the distal colons of rats with ulcerative colitis induced by the administration of 2,4,6-trinitrobenzene sulfonic acid (colitis group). The survival time after colitis induction was 24 h. The treated animals were compared to sham rats injected with phosphate-buffered saline and to animals with no intervention (control group). Tissues were prepared for immunohistochemical double-staining methods to examine P2X7 receptor, choline acetyltransferase (ChAT), calbindin, calretinin, anti-HuC/D (pan-neuronal) and S100β (pan-glial). The colocalization of the P2X7 receptor-immunoreactive (IR) cells was observed in the myenteric plexus with nitric oxide synthase (NOS)-, ChAT-,calbindin-, calretinin- and HuC/D-IR neurons and S100β-IR cells in the control, sham and colitis groups. The neuronal density (cell bodies/cm(2)) decreased in the myenteric plexus by 11, 18, 34, 22 and 60% in the P2X7 receptor, NOS-, ChAT-, calbindin- and calretinin-IR neurons, respectively. In addition, the densities (cell bodies/cm(2)) of HuC/D-IR neurons and S100β-IR enteric glial cells decreased by 33 and 29%, respectively. The profile areas were reduced by 6.8 and 21% in NOS- and ChAT-IR neurons, respectively. There was also a 20% increase of calbindin-IR neurons. Morphological changes were observed, such as increased neutrophils, disintegration of the intestinal epithelium and goblet cells and decreased collagen. This study demonstrated that colitis differentially affects P2X7 receptor-expressing enteric neurons based on their chemical codes and may cause changes in morphology and motility.

Purinergic drug targets for gastrointestinal disorders

“…Colitis differentially affects P2X7R-expressing enteric neurons based on their chemical codes (da Silva et al, 2015). P2X7R activation also triggers mucosal regulatory T cell death (Figliuolo et al, 2017).…”

Morphological Characterization of the Myenteric Plexus of the Ileum and Distal colon of Dogs Affected by Muscular Dystrophy

“…The presence of the P2X7 receptor in the myenteric neurons of DT dogs suggests its participation in many cellular processes, such as cell death and cell degeneration (Burnstock, 2014;Sperl agh and Illes, 2014). Other studies showed changes in the expression of this receptor, which was previously demonstrated in other animal species to be diminished in diseases such as intestinal ischemia/reperfusion (Paulino et al, 2011;Palombit et al, 2013), ulcerative colitis (Da Silva et al, 2015) and malnutrition (Girotti et al, 2013). However, to evaluate changes in P2X7 receptor expression in DT animals, it would be interesting to compare DT animals with control animals.…”

“…Following ischemia and reperfusion, the value for ChAT‐IR neurons was 341 μm 2 , and that for NOS‐IR neurons was 577 μm 2 . In ulcerative colitis, Da Silva et al () showed that the size of ChAT‐IR neurons in the distal colon of control rats was 458 μm 2 , and that of NOS neurons was 511 μm 2 ; in the colitis group, the size of ChAT‐IR neurons was 361 μm 2 , and that of NOS‐r neurons was 476 µm 2 . In addition, there are differences in neuron size between the ileum and distal colon in different species.…”

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“…A colite ulcerativa caracteriza-se como uma inflamação limitada ao colo, normalmente iniciando no reto e espalhando de maneira contínua. Conforme descrito na literatura, a colite ulcerativa apresenta inflamação superficial, limitada as regiões da mucosa e submucosa, associada a criptite e abscessos crípticos (SARTOR, 2006;KHOR et al, 2011;DA SILVA et al, 2015. Em nosso estudo, os tecidos do grupo Colite 24 horas apresentaram lesões, hiperemia, inflamação e presença de úlceras com extensão da lesão de 2 a 4 cm.…”

“…Os tecidos do grupo BBG 7 dias não apresentaram alterações macroscópicas. Foi observado resultados semelhantes em tecidos submetidos a colite (Da Silva et al, 2015).…”