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Published on: January 21, 2015
Effects of experimental ulcerative colitis on myenteric neurons in P2X7-knockout mice
Felipe Alexandre Machado1, Roberta Figueiroa Souza1, Vanessa Ribeiro Figliuolo2
1Department of Anatomy, Institute Biomedical and Sciences, University of São Paulo, Av. Prof. Dr. Lineu Prestes, 2415, São Paulo, CEP 05508-900, Brazil.
Abstract:
This study aimed to investigate the distal colon myenteric plexus and enteric glial cells (EGCs) in P2X7 receptor-deficient (P2X7-/-) animals after the induction of experimental ulcerative colitis. 2,4,6-Trinitrobenzene sulfonic acid (TNBS) was injected into the distal colon of C57BL/6 (WT) and P2X7 receptor gene-deficient (P2X7-/-, KO) animals. Distal colon tissues in the WT and KO groups were analyzed 24 h and 4 days after administration. The tissues were analyzed by double immunofluorescence of the P2X7 receptor with neuronal nitric oxide synthase (nNOS)-immunoreactive (ir), choline acetyltransferase (ChAT)-ir, and PGP9.5 (pan neuronal)-ir, and their morphology was assessed by histology. The quantitative analysis revealed 13.9% and 7.1% decreases in the number of P2X7 receptor-immunoreactive (ir) per ganglion in the 24 h-WT/colitis and 4 day-WT/colitis groups, respectively. No reduction in the number of nNOS-ir, choline ChAT-ir, and PGP9.5-ir neurons per ganglion was observed in the 4 day-KO/colitis group. In addition, a reduction of 19.3% in the number of GFAP (glial fibrillary acidic protein)-expressing cells per ganglion was found in the 24 h-WT/colitis group, and a 19% increase in the number of these cells was detected in the 4 day-WT/colitis group. No profile area changes in neurons were observed in the 24 h-WT and 24 h-KO groups. The 4 day-WT/colitis and 4 day-KO/colitis groups showed increases in the profile neuronal areas of nNOS, ChAT, and PGP9.5. The histological analysis showed hyperemia, edema, or cellular infiltration in the 24 h-WT/colitis and 4 day-WT/colitis groups. Edema was observed in the 4 day-KO/colitis group, which showed no histological changes compared with the 24 h-KO/colitis group. We concluded that ulcerative colitis differentially affected the neuronal classes in the WT and KO animals, demonstrating the potential participation and neuroprotective effect of the P2X7 receptor in enteric neurons in inflammatory bowel disease.
Insights
The P2X7 receptor plays a neuroprotective role in ulcerative colitis, as its deficiency exacerbates inflammation and alters enteric neuron function. This highlights the receptor
Area of Science:
- Gastroenterology and Neuroscience
- Inflammatory Bowel Disease Research
- Cellular and Molecular Biology
Background:
- The myenteric plexus and enteric glial cells (EGCs) are crucial for gut function.
- Ulcerative colitis (UC) involves inflammation affecting the colon.
- The P2X7 receptor's role in gut inflammation and neuronal function is not fully understood.
Purpose of the Study:
- To investigate the impact of P2X7 receptor deficiency on the distal colon myenteric plexus and EGCs during experimental ulcerative colitis.
- To elucidate the potential neuroprotective mechanisms of the P2X7 receptor in inflammatory bowel disease.
Main Methods:
- Experimental ulcerative colitis was induced using TNBS in wild-type (WT) and P2X7 receptor-deficient (P2X7-/-) mice.
- Distal colon tissues were analyzed at 24 hours and 4 days post-induction.
- Immunofluorescence staining was used to assess P2X7 receptor, nNOS, ChAT, PGP9.5, and GFAP expression.
- Histological analysis evaluated tissue damage and inflammatory markers.
Main Results:
- P2X7 receptor expression decreased in WT mice with colitis.
- P2X7 deficiency (KO) prevented the reduction in nNOS, ChAT, and PGP9.5-immunoreactive neurons observed in WT colitis.
- GFAP-expressing cells (EGCs) showed altered numbers in WT colitis but were less affected in P2X7-deficient mice.
- Histological analysis revealed more severe inflammation in WT colitis compared to P2X7-deficient colitis.
Conclusions:
- Ulcerative colitis differentially affects neuronal populations in the presence and absence of the P2X7 receptor.
- The P2X7 receptor appears to have a neuroprotective role in enteric neurons during inflammatory bowel disease.
- Targeting the P2X7 receptor may offer therapeutic potential for managing inflammatory bowel disease.
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