Neuronal plasticity of the enteric nervous system is correlated with chagasic megacolon development

Silveira, Alexandre Barcelos Morais da; Freitas, Michelle A. R.; Oliveira, Ênio Chaves de; Neto, Salustiano Gabriel; Luquetti, Alejandro O.; Furness, John B.; Correa-Oliveira, Rodrigo; Reis, Débora d’Ávila

doi:10.1017/s0031182008004770

Cited by 25 publications

(26 citation statements)

References 28 publications

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“…In fact, in chagasic megacolon, inhibitory motor neurons (VIP and NOS immunoreactive) are preferentially destroyed. This may explain, at least in part, the partial inability of the involved colon and internal anal sphincter to relax, which seems to induce a mechanical obstruction and dilation of the organ (da Silveira et al 2007b, 2008b). …”

Section: The Role Of Different Cell Populations and Cytokines In Estamentioning

confidence: 99%

Cellular and genetic mechanisms involved in the generation of protective and pathogenic immune responses in human Chagas disease

Dutra¹,

Menezes

Villani³

et al. 2009

Mem. Inst. Oswaldo Cruz

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Perhaps one of the most intriguing aspects of human Chagas disease is the complex network of events that underlie the generation of protective versus pathogenic immune responses during the chronic phase of the disease. While most individuals do not develop patent disease, a large percentage may develop severe forms that eventually lead to death. Although many efforts have been devoted to deciphering these mechanisms, there is still much to be learned before we can fully understand the pathogenesis of Chagas disease. It is clear that the host’s immune response is decisive in this process. While characteristics of the parasite influence the immune response, it is becoming evident that the host genetic background plays a fundamental role in the establishment of pathogenic versus protective responses. The involvement of three complex organisms, host, parasite and vector, is certainly one of the key aspects that calls for multidisciplinary approaches towards the understanding of Chagas disease. We believe that now, one hundred years after the discovery of Chagas disease, it is imperative to continue with highly interactive research in order to elucidate the immune response associated with disease evolution, which will be essential in designing prophylactic or therapeutic interventions.

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Section: The Role Of Different Cell Populations and Cytokines In Estamentioning

confidence: 99%

Cellular and genetic mechanisms involved in the generation of protective and pathogenic immune responses in human Chagas disease

Dutra¹,

Menezes

Villani³

et al. 2009

Mem. Inst. Oswaldo Cruz

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“…T. cruzi also invades neurons in both the PNS and CNS (38,40). The interaction of T. cruzi with the nervous system may trigger cell survival mechanisms, as judged by nerve tissue-regenerative events in patients in the chronic indeterminate phase of Chagas' disease (16,17,25). For example, although the number of neurons in chagasic patients is lower than that of age-matched healthy individuals, the average number of neurons in both cardiac and gastrointestinal ganglia actually increases with the age of patients, contrary to the age-related physiological reduction in nonchagasic individuals (25).…”

mentioning

confidence: 99%

Trypanosoma cruziPromotes Neuronal and Glial Cell Survival through the Neurotrophic Receptor TrkC

Weinkauf

PereiraPerrin

2009

Infect Immun

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Trypanosoma cruzi, the agent of Chagas' disease, promotes neuron survival through receptor tyrosine kinase TrkA and glycosylphosphatidylinositol-anchored glial cell-derived family ligand receptors (GFR␣). However, these receptors are expressed by only a subset of neurons and at low levels or not at all in glial cells. Thus, T. cruzi might exploit an additional neurotrophic receptor(s) to maximize host-parasite equilibrium in the nervous system. We show here that T. cruzi binds TrkC, a neurotrophic receptor expressed by glial cells and many types of neurons, and that the binding is specifically inhibited by neurotrophin-3, the natural TrkC ligand. Coimmunoprecipitation and competition assays show that the trans-sialidase/parasite-derived neurotrophic factor (PDNF), previously identified as a TrkA ligand, mediates the T. cruzi-TrkC interaction. PDNF promotes TrkC-dependent mitogen-activated protein kinase signaling, neurite outgrowth, and survival of genetically engineered PC12 neuronal cells and glial Schwann cells in a TrkC-dependent manner. Thus, TrkC is a new neurotrophic receptor that T. cruzi engages to promote the survival of neuronal and glial cells. The results raise the possibility that T. cruzi recognition of TrkC underlies regenerative events in nervous tissues of patients with Chagas' disease.

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“…Patients may show signs of neuroregeneration and/or neuroprotection, such as an age-dependent relative increase in the number of ganglion cells in the heart and enteric nervous system (23). Neuroregeneration in the enteric nervous system may occur even in chagasic megacolon (13).…”

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confidence: 99%

Preferential Brain Homing following Intranasal Administration ofTrypanosoma cruzi

Caradonna

PereiraPerrin

2009

Infect Immun

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The Chagas' disease parasite Trypanosoma cruzi commonly infects humans through skin abrasions or mucosa from reduviid bug excreta. Yet most studies on animal models start with subcutaneous or intraperitoneal injections, a distant approximation of the skin abrasion route. We show here that atraumatic placement of T. cruzi in the mouse nasal cavity produced low parasitemia, high survival rates, and preferential brain invasion compared to the case with subcutaneously injected parasites. Brain invasion was particularly prominent in the basal ganglia, peaked at a time when parasitemia was no longer detectable, and elicited a relatively large number of inflammatory foci. Yet, based on motor behavioral parameters and staining with Fluoro-Jade C, a dye that specifically recognizes apoptotic and necrotic neurons, brain invasion did not cause neurodegenerative events, in contrast to the neurodegeneration in the enteric nervous system. The results indicate that placement of T. cruzi on the mucosa in the mouse nasal cavity establishes a systemic infection with a robust yet harmless infection of the brain, seemingly analogous to disease progression in humans. The model may facilitate studies designed to understand mechanisms underlying T. cruzi infection of the central nervous system.

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Neuronal plasticity of the enteric nervous system is correlated with chagasic megacolon development

Cited by 25 publications

References 28 publications

Cellular and genetic mechanisms involved in the generation of protective and pathogenic immune responses in human Chagas disease

Cellular and genetic mechanisms involved in the generation of protective and pathogenic immune responses in human Chagas disease

Trypanosoma cruziPromotes Neuronal and Glial Cell Survival through the Neurotrophic Receptor TrkC

Preferential Brain Homing following Intranasal Administration ofTrypanosoma cruzi

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