Caracterização da relação entre a expressão de serotonina e o processo regenerativo em neurônios do sistema nervoso entérico de paciente chagásicos com megacólon

Abstract

The digestive form resulting from Chagas´ disease is one of the main causes of morbidity and mortality in the chronic phase of the disease. Patients with the digestive form have a series of symptoms related to organ obstruction. In the megacolon, the organs exhibit a large increase in the lumen and hypertrophy of the muscle layer. Histological analyzes of the affected organs have shown inflammatory lesions of the enteric nervous system (ENS), associated with a large reduction in the number of neurons. Although the mechanism of neuronal injury remains unclear, the frequent observation of ganglionitis and peri-ganglionitis in patients with mega points to the participation of immune cells in this process. Individuals without mega also presented denervation and inflammation processes, however less intense in relation to megacolon carriers. These data open a new line of investigation on the study of the chagasic megacolon pathology. To understand the development of this pathology, we must evaluate not only the degree of destruction of the different neuronal classes, but also the rate of regeneration and the substances involved in this process. For this, we used a marker for regeneration of neurons and nerve endings (GAP43) associated with a pan-neuronal marker (Peripherin) and with a serotonin marker in the intestine in chagasic patient groups with megacolon, without megacolon and uninfected individuals. Our results demonstrated that chagasic patients without megacolon have a higher expression of serotonin and GAP43 in their nerve plexuses compared to patients with megacolon and uninfected individuals. These results suggest that this process of neuronal plasticity occurs in the colon of patients with chronic infection by Trypanosoma cruzi and may be directly related to the expression of serotonin by SNE, which would be decisive for the development of the megacolon or for the permanence in the indeterminate phase of the disease. Thus, the data in this work indicate that the development of the chagasic megacolon is closely related to the regenerative capacity of neurons of the enteric nervous system in the entire gastrointestinal tract and that this regenerative capacity is linked to the expression of intestinal serotonin.