Chagasic megacolon: enteric neurons and related structures

Area of Science:

• Gastroenterology
• Neuroscience
• Pathology

Background:

• Megacolon, or colonic dilation, is linked to gastrointestinal disorders, including Chagas disease.
• In Chagas disease, megacolon is characterized by pathohistological changes and massive myenteric neuron loss.
• This neuron loss is selective, sparing some inhibitory neurons like those containing neuronal nitric oxide synthase and vasoactive intestinal peptide (VIP).

Purpose of the Study:

• To investigate the correlation between neuron survival, muscle elements, and interstitial cells of Cajal in Chagasic megacolon.
• To assess the role of specific neuronal populations, particularly VIP- and calretinin-immunoreactive neurons, in maintaining colonic function and patient survival.

Main Methods:

• Histopathological analysis of surgically resected megacolonic segments.
• Immunohistochemical estimation of α-smooth muscle actin and c-kit profiles to assess muscle and interstitial cell densities.
• Evaluation of neuron loss in both myenteric and submucosal plexuses, with a focus on VIP- and calretinin-expressing neurons.

Main Results:

• Decreased densities of α-smooth muscle actin and c-kit were observed in dilated megacolonic zones compared to transitional zones.
• The myenteric plexus showed significant neuron loss, while the submucosal plexus had moderate neuron loss.
• Neurons co-immunoreactive for VIP and calretinin exhibited disproportionate survival.

Conclusions:

• Disproportionate survival of VIP- and calretinin-expressing neurons may preserve epithelial barrier function and contribute to long-term survival in Chagasic patients.
• VIP's neuroprotective and neuroeffectory functions suggest a critical role in the pathogenesis and progression of Chagasic megacolon.
• While colonic motility is severely disturbed, specific neuronal survival mechanisms allow for prolonged patient survival despite megacolon.