Targeting hypothalamus: diet impact, bacterial composition and memory impair

• Autor(a) principal: Várzea, Bruno André Martins
• Data de Publicação: 2020
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.1/14696
• topic: Hipotálamo; Colesterol; Dieta; Microbiota intestinal; Inflamação intestinal; Memória; Domínio/Área Científica::Ciências Médicas::Outras Ciências Médicas

Cholesterol metabolism is critical for neuronal functions such as, myelin formation, neurotransmitters release, membrane repair and also synaptogenesis, in the Central Nervous System (CNS), and its homeostasis is mainly maintained by CYPX. This enzyme catalyses the conversion of cholesterol into X-Hydroxycholesterol (X-HC) and may be a useful marker of neurodegenerative diseases. The X-HC is able to cross the blood-brain-barrier (BBB) into the circulation, having possible roles in the overall bile acid synthesis in the liver, therefore having an indirect impact on intestinal microbiota within human Gastrointestinal tract (GI). In the other hand, a diet mainly rich in fat, carbohydrates and protein, a typical Western diet, have been highly associated with changes in the GI environment, promoting alterations in intestinal microbiota composition, termed as dysbiosis, being associated with early metabolic physiopathological changes, such as increased intestinal barrier permeability and a state of low-grade intestinal inflammation. The main objective of this study was to determine the effects of either Cyp overexpression and silencing treatment and diet on intestinal bacterial groups, cognitive abilities and also on colon health status. C57BL/J6 mice were fed with either chow diet or an High Fat Diet (HFD), for 12 weeks. To determine the effects caused by both Cyp overexpression and silencing and also by the HFD and Control diet on the intestinal bacteriome, the quantification of several intestinal bacterial groups was performed using qPCR. The targeted bacterial groups included Bacteroidetes, Firmicutes, Sulphate-Reducing Bacteria (SRB), Betaproteobacteria, Delta-and Gammaproteobacteria, Actinobacteria and Tenericutes. The exposure of mice to an HFD resulted in variations in the loads of the intestinal bacteria. Interestingly, the Cyp silencing lead to an approximation of intestinal bacterial loads between mice exposed to the different diets. The Cyp silencing resulted in a decreased performance in Y-maze spontaneous alternation test, within subjects with a chow diet. In addition, both Cyp overexpression and silencing in mice exposed to an HFD showed increased signs of intestinal inflammation. Taken together, this study showed that intestinal microbiota is mainly influenced by dietary factors.