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

Nascimento, Rodolfo Duarte; Martins, Patrícia; Duarte, Jacqueline Garcia; Reis, Débora d’Ávila

doi:10.23937/2469-5807/1510059

Cited by 2 publications

(2 citation statements)

References 33 publications

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“…No evidence of altered transcript abundance was found for markers of other enteric neuronal subtypes, tyrosine hydroxylase ( Th ) and choline acetyltransferase ( Chat ), tropomyosin receptor kinases ( Ntrk1 /2/3) or nerve growth factor receptor ( Ngfr ). Taken together, these data indicate a possible downregulation of the enteric nitrergic transmission associated with GI dysfunction in DCD mice, recapitulating observations in human Chagas megasyndromes as well as other enteric neuropathies [ 16 , 33 – 36 ].…”

Section: Resultssupporting

confidence: 81%

Local association of Trypanosoma cruzi chronic infection foci and enteric neuropathic lesions at the tissue micro-domain scale

et al. 2021

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Digestive Chagas disease (DCD) is an enteric neuropathy caused by Trypanosoma cruzi infection. The mechanism of pathogenesis is poorly understood and the lack of a robust, predictive animal model has held back research. We screened a series of mouse models using gastrointestinal tracer assays and in vivo infection imaging systems to discover a subset exhibiting chronic digestive transit dysfunction and significant retention of faeces in both sated and fasted conditions. The colon was a specific site of both tissue parasite persistence, delayed transit and dramatic loss of myenteric neurons as revealed by whole-mount immunofluorescence analysis. DCD mice therefore recapitulated key clinical manifestations of human disease. We also exploited dual reporter transgenic parasites to home in on locations of rare chronic infection foci in the colon by ex vivo bioluminescence imaging and then used fluorescence imaging in tissue microdomains to reveal co-localisation of infection and enteric nervous system lesions. This indicates that long-term T. cruzi-host interactions in the colon drive DCD pathogenesis, suggesting that the efficacy of anti-parasitic chemotherapy against chronic disease progression warrants further pre-clinical investigation.

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Section: Resultssupporting

confidence: 81%

Local association of Trypanosoma cruzi chronic infection foci and enteric neuropathic lesions at the tissue micro-domain scale

et al. 2021

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“…No evidence of altered transcript abundance was found for markers of other enteric neuronal subtypes, tyrosine hydroxylase (Th) and acetylcholine (Chat), tropomyosin receptor kinases (Ntrk1/2/3) or nerve growth factor (Ngfr). Taken together, these data indicate a possible downregulation of the enteric nitrergic transmission associated with GI dysfunction in DCD mice, recapitulating observations in human Chagas megasyndromes as well as other enteric neuropathies [19][20][21][22][23] .…”

Section: Regional Dissection Of the Transit Delay Phenotype Reveals Lsupporting

confidence: 80%

Local association ofTrypanosoma cruzichronic infection foci and enteric neuropathic lesions at the tissue micro-domain scale

Khan¹,

Langston

Costa

et al. 2021

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Gastrointestinal (GI) disease affects a substantial subset of chronic Chagas disease (CD) patients, but the mechanism of pathogenesis is poorly understood. The lack of a robust, predictive animal model of chronic T. cruzi infection that exhibits functional digestive disease has held back research. To address this, we combined GI tracer assays and bioluminescence in vivo infection imaging systems for diverse parasite strains to discover models exhibiting chronic digestive transit dysfunction. We identified the colon as a specific site of both tissue parasite persistence and delayed transit. Digestive CD mice exhibited significant retention of faeces in both sated and fasted conditions. Histological and immunofluorescence analysis of the enteric nervous system (ENS) revealed a dramatic reduction in the number of neurons and a loss of immunoreactivity of the enteric neural network in the colon. This model therefore recapitulates key clinical manifestations of human digestive CD. We also exploited dual bioluminescent-fluorescent parasites to analyse rare chronic infection foci in the colon at the single cell level, revealing co-localisation with ENS lesions. This indicates that long-term T. cruzi-host interactions in the colon drive pathogenesis and thus chronic disease may be preventable using anti-parasitic chemotherapy.

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

Cited by 2 publications

References 33 publications

Local association of Trypanosoma cruzi chronic infection foci and enteric neuropathic lesions at the tissue micro-domain scale

Local association of Trypanosoma cruzi chronic infection foci and enteric neuropathic lesions at the tissue micro-domain scale

Local association ofTrypanosoma cruzichronic infection foci and enteric neuropathic lesions at the tissue micro-domain scale

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