P2X7 receptor antagonist recovers ileum myenteric neurons after experimental ulcerative colitis.

Abstract

BACKGROUND The P2X7 receptor is expressed by enteric neurons and enteric glial cells. Studies have demonstrated that administration of a P2X7 receptor antagonist, brilliant blue G (BBG), prevents neuronal loss. AIM To report the effects of BBG in ileum enteric neurons immunoreactive (ir) following experimental ulcerative colitis in Rattus norvegicus albinus. METHODS 2,4,6-trinitrobenzene sulfonic acid (TNBS group, n = 5) was injected into the distal colon. BBG (50 mg/kg, BBG group, n = 5) or vehicle (sham group, n = 5) was given subcutaneously 1 h after TNBS. The animals were euthanized after 24 h, and the ileum was removed. Immunohistochemistry was performed on the myenteric plexus to evaluate immunoreactivity for P2X7 receptor, neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), HuC/D and glial fibrillary acidic protein. RESULTS The numbers of nNOS-, ChAT-, HuC/D-ir neurons and glial fibrillary acidic protein-ir glial cells were decreased in the TNBS group and recovered in the BBG group. The neuronal profile area (μm2) demonstrated that nNOS-ir neurons decreased in the TNBS group and recovered in the BBG group. There were no differences in the profile areas of ChAT- and HuC/D-ir neurons. CONCLUSION Our data conclude that ileum myenteric neurons and glial cells were affected by ulcerative colitis and that treatment with BBG had a neuroprotective effect. Thus, these results demonstrate that the P2X7 receptor may be an important target in therapeutic strategies.