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

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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/cm2) 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/cm2) 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.

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Acknowledgments

We thank Rosana Prisco for performing the statistical analysis. These studies were supported by the São Paulo Research Foundation (FAPESP/Fundação de Amparo à Pesquisa do Estado de São Paulo) and the CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico).

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  1. Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Dr. Lineu Prestes, 2415, São Paulo, CEP 05508-900, Brazil

    Marcos Vinícius da Silva, Aline Rosa Marosti, Cristina Eusébio Mendes, Kelly Palombit & Patricia Castelucci

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  1. Marcos Vinícius da Silva
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  2. Aline Rosa Marosti
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  3. Cristina Eusébio Mendes
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  4. Kelly Palombit
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  5. Patricia Castelucci
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Correspondence to Patricia Castelucci.

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da Silva, M.V., Marosti, A.R., Mendes, C.E. et al. Differential effects of experimental ulcerative colitis on P2X7 receptor expression in enteric neurons. Histochem Cell Biol 143, 171–184 (2015). https://doi.org/10.1007/s00418-014-1270-6

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