Neurodegeneração no plexo mioentérico do intestino grosso : Estudo em diferentes modelos experimentais

• Ano de defesa: 2016
• Autor(a) principal: Beraldi, Evandro José
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Estadual de Maringá; Brasil; Programa de Pós-Graduação em Ciências Biológicas; UEM; Maringá, PR; Centro de Ciências Biológicas
• Palavras-chave em Português: Sistema nervoso entérico; Obesidade; Dieta hiperlipídica; Diabetes; Resveratrol; Brasil.; Ciências Biológicas; Bioquímica
• Link de acesso: http://repositorio.uem.br:8080/jspui/handle/1/1871

Diabetes and obesity are conditions commonly associated with gastrointestinal disorders. Obesity is usually linked to delayed intestinal motility and high-fat diets cause loss of myenteric neurons in the small and large intestine, a reduction attributed to changes in the microbiota associated with inflammation. In diabetes, diarrhea and abdominal pain are frequent complications. The abnormal functioning of the gastrointestinal tract indicates complications and damage to the enteric nervous system, especially in the myenteric plexus, responsible for the intrinsic motor innervation. In addition to the microbiota, oxidative stress is indicated as a major cause of neurodegenerationand antioxidants can reduce the damaging effects of diabetes in the body. In the first study, we investigated if supplementation of a DHL with inulin, a prebiotic mainly metabolized in the colon by the microbiota, is able to modulate the bacterial populations toward the prevalence of communities considered less harmful to the body. We also investigated different myenteric neuronal populations to assess whether the neuronal loss could be mitigated and to analyze the association of innervation with colonic motility. In the second study, we investigated if treatment with resveratrol in rats with experimental diabetes is capable of acting attenuating the damage to the myenteric innervation of the colon, since resveratrol is a compound with proven antioxidant capacity. In the obesity study, Swiss mice were fed a purified diet for rodents or a high-fat diet (59% kcal fat), or the diets supplemented with inulin for 17 weeks. We investigated the intestinal and colonic motility, blood biochemical measurements, metagenomic analysis of colonic microbiota and gene expression levels of the inflammatory markers TNF-α, IL6 and IL1B. We also performed immunofluorescence techniques for analysis of the neuronal density and cell body morphometry of different types of myenteric neurons of the distal colon, such as populations positive for myosin-V neuronal nitric oxide synthase, vasoactive intestinal peptide and calretinin. In the study with experimental diabetes, rats with streptozotocin-induced diabetes were treated with resveratrol (10 mg / kg) for 17 weeks. We evaluated physiological parameters and analyzed the neuronal density and cell body morphometry in the myenteric plexus of the distal colon, by immunofluorescence techniques. High-fat diet caused obesity and delayed colonic motility. The loss of myenteric neurons in the distal colon of obese animals affected all populations studied, with reduction in neuronal density of myosin-V, neuronal nitric oxide synthase, vasoactive intestinal peptide and calretinin positive neurons. This loss was accompanied by alterations in neuronal cell body size in some of the studied subpopulations. In particular, calretinin positive neurons appear to be more sensitive to the effects of the diet. Although obese animals supplemented with inulin had improved colonic motility, neuronal loss remained constant. Both the high-fat diet and the supplementation with inulin did not alter the metagenomic profile of the intestinal tract or the expression levels of inflammatory cytokines in the colon. In diabetic rats, we observed typical symptoms of the experimental model such as high blood glucose levels, body weight loss and increased speed of gastrointestinal transit, and neurodegeneration in the total population and nitrergic subpopulation. Resveratrol was not able to completely prevent neuronal loss, but mitigated in part the damage to myenteric neurons in the treated diabetic group, indicating its antioxidant and neuroprotective role. Although the treatment did not reduce the blood glucose of diabetic animals, some physiological parameters were improved such as weight loss and water consumption. High-fat diet or supplementation with inulin for a long time did not change the intestinal microbiota or gene expression levels of inflammatory markers in the distal colon of Swiss mice, indicating that the animals of this lineage are apparently more resistant to changes caused by diet these parameters. Nevertheless, obese mice showed neuronal loss in all studied neuronal populations, with consequently delayed colonic motility. In diabetic rats, resveratrol treatment minimized the damage to neurons in the distal colon, although it did not totally prevented neuronal loss in the myenteric plexus. Furthermore, resveratrol improved some characteristic physiological parameters of the disease.