Journal
JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY
Volume 28, Issue 3, Pages 483-500Publisher
KOREAN SOC NEUROGASTROENTEROLOGY & MOTILITY
DOI: 10.5056/jnm21074
Keywords
Acetylcholine; Enteric nervous system; Gastrointestinal motility; Megacolon; Trypanosoma cruzi
Categories
Funding
- CNPq [311976/2021-2]
- Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) [CDS-PPM 000304/16, PRONEX 305952/2017, PPM 00304-16, CBB-APQ-01419-14, APQ-00921-18]
- CAPES/Brazil
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This study investigated the effect of T. cruzi-induced progressive colonic structural changes on colonic contractile pattern activity. The results showed impaired intestinal motility and cholinergic system response in Chagasic megacolon.
Background/Aims Chagasic megacolon is caused by Trypanosoma cruzi, which promotes in several cases, irreversible segmental colonic dilation. This alteration is the major anatomic-clinical disorder, characterized by the enteric nervous system and muscle wall structural damage. Herein, we investigate how T. cruzi-induced progressive colonic structural changes modulate the colonic contractile pattern activity. Methods We developed a murine model of T. cruzi-infection that reproduced long-term modifications of the enlarged colon. We evaluated colonic and total intestinal transit time in animals. The patterns of motor response at several time intervals between the acute and chronic phases were evaluated using the organ bath assays. Enteric motor neurons were stimulated by electric field stimulation. The responses were analyzed in the presence of the nicotinic and muscarinic acetylcholine receptor antagonists. Western blot was performed to evaluate the expression of nicotinic and muscarinic receptors. The neurotransmitter expression was analyzed by real-time polymerase chain reaction. Results In the chronic phase of infection, there was decreased intestinal motility associated with decreased amplitude and rhythmicity of intestinal contractility. Pharmacological tests suggested a defective response mediated by acetylcholine receptors. The contractile response induced by acetylcholine was decreased by atropine in the acute phase while the lack of its action in the chronic phase was associated with tissue damage, and decreased expression of choline acetyltransferase, nicotinic subunits of acetylcholine receptors, and neurotransmitters. Conclusions T. cruzi-induced damage of smooth muscles was accompanied by motility disorders such as decreased intestinal peristalsis and cholinergic system response impairment. This study allows integration of the natural history of Chagasic megacolon motility disorders and opens new perspectives for the design of effective therapeutic. (J Neurogastroenterol Motil 2022;28:483-500)
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