Neurochemical Coding of the Enteric Nervous System in Chagasic Patients with Megacolon

Abstract

Neuronal destruction has been considered the hallmark of pathogenic mechanisms in chagasic megacolon. Characterization of neuropeptides in the enteric nervous system from chagasic patients with megacolon could elucidate some aspects of the development of this syndrome. In the present work we demonstrate the changes in expression of neuropeptides and neurochemical markers present in neuronal plexuses from the colons of chagasic patients with megacolon. Sections of frozen tissue samples were immunohistochemically labeled for anticalretinin, cChaT, substance P, VIP, NOS, and NPY. Immunoreactivity was observed using a confocal microscope. Our results demonstrate that in chagasic patients with megacolon, inhibitory motor neurons (VIP and NOS immunoreactive) are preferentially destroyed by Trypanosoma cruzi and/or the inflammatory process. These results suggest a selective destruction of enteric neurons in the colon of chagasic patients with megacolon, pointing to an important discovery in the mechanism of pathogenesis of Chagas' disease.

Decrease of Nitrergic Innervation in the Esophagus of Patients with Chagas Disease: Correlation with Loss of Interstitial Cells of Cajal

“…It is well known that, like other cells, the number of ICCs is controlled by several factors that regulate proliferation and death and that ICCs continuously undergo apoptosis in the GI tract of healthy individuals [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. Because neurons produce Stem Cell Factor (SCF), which activates the c-kit receptor and stimulates the proliferation, survival…”

“…It is well known, however, that motility regulation in the GI tract and lower esophageal sphincter relaxation is influenced not only by neuromediators, as Nitric Oxide (NO), but also by Interstitial Cells of Cajal (ICCs) [10][11][12][13]. ative decrease in the number of neurons in colon of chagasic patient with megacolon [25].…”

Assessment of Rectocolonic Morphology and Function in Patients with Chagas Disease in Barcelona (Spain)

“…19 The high proportion of symptomatic Chagas disease patients with anorectal motility abnormalities would appear to suggest that chronic T. cruzi infection has induced neuronal damage in these individuals, as observed by other authors. 20,21 However, in selected groups of constipated individuals it has been previously shown that the majority of them have impaired relaxation of the anal sphincter during the defecatory maneuvers. A similar pattern was observed in our control population of constipated non-Chagas disease individuals, about 90% of whom showed abnormal anorectal manometry.…”

The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

“…The most damaging and established sequel is that of fatal cardiomyopathy, however the digestive tract is also commonly affected with extensive destruction of ganglion cells (Ribeiro et al 1998;da Silveira et al 2007) leading to altered motility manifest as functional obstruction with eventual progression to hypertrophy of the smooth muscle and marked dilatation (i.e. megaoesophagus and megacolon) (Koberle 1968).…”

“…Regarding the investigation of serum effects on colonic smooth muscle tone, in vitro experiments have used muscle taken from either normal rat colon or human chagasic megacolon samples, reporting very similar responses to incubation with chagasic serum in both tissues. This result is curious as inter-species variability in colonic muscarinic receptor profile appears to exist (Gomez et al 1992) and chagasic megacolon is characterised by extensive damage to the neuromuscular apparatus including (Corbett et al 2001;da Silveira et al 2007). Our cellbased assay designed to detect anti-M 2 mAChR IgG failed to detect these autoantibodies in a cohort of Chagas' disease patients.…”