Effect of Anti-TNF Monoclonal Antibody on Enteric Neurons and Enteric Glial Cells in Experimental Colitis

Author(s)

Souza, Roberta Figueiroa ; Machado, Felipe Alexandre ; Caetano, Marcos Antonio Ferreira ; De Paulo, Caroline Bures ; Castelucci, Patricia

• Document type: Journal article
• Source: Digestive Diseases and Sciences; v. N/A, p. 20-pg., 2025-02-13.

Abstract

BackgroundInflammatory bowel diseases (IBD) affect both enteric neurons and enteric glia, with tumor necrosis factor-alpha (TNF-alpha) playing a role as an inflammatory mediator.AimsAnalyze the effects of the anti-TNF monoclonal antibody on the myenteric plexus in an experimental model of colitis.MethodsC57BL/6 mice received 3% dextran sodium sulfate (DSS) in drinking water for 7 days in both the DSS and DSS + ADA groups. The Sham group received water. The DSS + ADA group received ADA anti-TNF-alpha on day 2 of DSS intake. The ADA group was given water throughout the period and received an anti-TNF-alpha injection on day 2. The study evaluated the number of neurons per ganglion, and the area of the neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), pan-neuronal marker (PGP9.5), and tumor necrosis factor receptor 2 (TNFR2) immunoreactive (-ir). Double labeling of PGP9.5 with an enteric glial marker (GFAP) was also performed.ResultsDSS successfully induced experimental colitis (EC). TNFR2 was detected in the myenteric neurons in all groups. EC affected the enteric neurons, showing a decrease in the number of TNFR2-ir, ChAT-ir, nNOS-ir, and PGP9.5-ir neurons, whereas enteric glial cells increased in both the DSS and DSS + ADA groups. The DSS + ADA group showed number of nNOS-ir, ChAT-ir, and PGP9.5-ir neurons per ganglion similar to Sham group. EC also affected the neuronal profile, resulting in smaller areas in the DSS and DSS + ADA groups.ConclusionMyenteric neurons are immunoreactive to the TNFR2. DSS altered the myenteric plexus, and anti-TNF monoclonal antibody treatment proved effective against EC due to preventing the pathology from developing. (AU)

• FAPESP's process: 23/03973-1 - Study of enteric neurons and enteric glial cells in Chronic Experimental Ulcerative Colitis in mice deficient for the P2X7 receptor (P2X7R-/-)
• Grantee: Roberta Figueiroa de Souza
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 22/14406-8 - Characterization of the effect of sodium butyrate on short-chain fatty acid receptors in the enteric nervous system of mice submitted to experimental ulcerative colitis
• Grantee: Marcos Antônio Ferreira Caetano
• Support Opportunities: Scholarships in Brazil - Doctorate