Submitted by Celso Magalhaes (celsomagalhaes@ufrrj.br) on 2017-08-22T12:11:35Z No. of bitstreams: 1 2016 - Erica Bertha Fuhrich Raupp Bezerra de Mello.pdf: 1405623 bytes, checksum: 5fa531efb35b7236db276d4de4b56a2e (MD5) / Made available in DSpace on 2017-08-22T12:11:35Z (GMT). No. of bitstreams: 1 2016 - Erica Bertha Fuhrich Raupp Bezerra de Mello.pdf: 1405623 bytes, checksum: 5fa531efb35b7236db276d4de4b56a2e (MD5) Previous issue date: 2016-10-25 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Increased indicators of fat metabolism are found in Equine Metabolic Syndrome (EMS) subjects although these symptons are not included in the EMS definition described in the literature and in its diagnosis. 18 mares were allocated in three groups according to body condition status. In Group Ideal there were animals in fit condition (n=6), in Group Overweight, considered in overweight (n=6) and in Group Obese (n=6), animals considered obese. Fasting blood samples were taken to determine triglycerides, total cholesterol, glucose, and insulin concentrations in plasma. Insulin sensitivity proxy (RISQI) and ?-pancreatic secretion proxy (MIRG) were calculated from glucose and insulin data. There was a difference between groups in triglycerides levels (p<0.01), where Group Obese had significantly higher concentrations than other groups. Total cholesterol was higher in Group Obese compared to Group Ideal (p=0.01). No differences in plasma glucose (p=0.53) nor insulin (p = 0.10) concentrations and insulin sensitivity (RISQI: p=0.46) were seen among groups. Group Obese had a higher ?-pancreatic secretion (MIRG: p=0.05) compared to Group Ideal. The increased body condition score influenced the results of fat metabolites and ?-pancreatic secretion / O aumento das concentra??es de indicadores do metabolismo de gorduras ? bastante comum em casos diagnosticados de S?ndrome Metab?lica Equina (SME), mas apesar disto n?o entra no hall de fatores determinantes para diagn?stico da SME. Para avaliar a influ?ncia do escore corporal (EC) nas altera??es secund?rias associadas ? SME, foram avaliados lipidograma, glicemia, concentra??o de insulina, sensibilidade ? insulina (RISQI) e secre??o ?-pancre?tica de tr?s grupos de de ?guas Mangalarga Marchador n?o-getsantes/n?o-lactantes em tr?s diferentes categorias de EC (Ideal, Sobrepeso e Obeso). Cada grupo contou com 6 animais. Foram coletadas amostras de sangue em jejum de concentrado para a determina??o de concentra??o plasm?tica de triglicer?deos, colesterol total, glicose e insulina e a partir dos valores de glicemia e insulinemia foram calculados valores preditivos de sensibilidade ? insulina (RISQI) e secre??o ?-pancre?tica (MIRG). Houve diferen?a estat?stica entre os grupos quando avaliado os n?veis de triglicer?deos (p<0,01), sendo que o Grupo Obeso apesentou resultados significativamente superiores aos demais grupos. Foi observada diferen?a estat?stica entre os grupos quando avaliado as concentra??es de colesterol total (p=0,01), sendo que o Grupo Obeso apresentou resultados significativamente superiores ao Grupo Ideal. N?o foi observada diferen?a estat?stica entre os grupos nas concentra??es plasm?ticas de glicose (p=0,53) e insulina (p=0,10). N?o foi observada diferen?a estat?stica nos valores obtidos de RISQI (p=0,46), mas houve diferen?a estat?stica entre os grupos nos valores obtidos de MIRG (p=0,05), sendo que o Grupo Obeso obteve resultados significativamente superiores quando comparado com o Grupo Ideal. O escore corporal influenciou de forma positiva nos resultados do lipidograma e valor preditivo de secre??o ?-pancre?tica, sendo encontrados maiores n?veis em animais obesos.

Après le vieillissement, le diabète Mellitus de type 2 (DMT2) est le facteur de risque le plus important pour développer la maladie d'Alzheimer (MA). Le DMT2 est une maladie métabolique caractérisée par une hyperglycémie et une résistance à l’insuline qui se développe vers la cinquantaine et est fortement favorisée par l’obésité. Nous avons exploré l’impact potentiel du DMT2 sur le développement de la MA chez le Rat. Pour cela, nous avons utilisé un régime alimentaire cafétéria (RC) couplé à des injections de faibles doses de Streptozotocine (STZ) (STZ-CD). Les rats STZ-CD montrent des signes classiques de DMT2 et des déficits légers de consolidation en mémoire de reconnaissance spatiale. Afin d'imiter le développement des stades précoces de la MA, la moitié des rats reçoivent une infusion intracérébrale de peptides β-amyloïdes solubles (Aβ) qui ne conduisent pas à des déficits mnésiques durables. Par contre, le phénotype DMT2 chez les rats STZ-CD exacerbe les déficits mnésiques observés avec le peptide Aβ en les prolongeant dans le temps. L’enrichissement environnemental pendant une période critique de 2 semaines après l’infusion d’Aβ est capable de compenser les déficits mnésiques induits par le peptide Aβ et/ou le traitement STZ-CD ; mais d’une manière limitée dans le temps. Des analyses biochimiques dans l’aire CA1 de l’hippocampe ont été effectuées pour explorer de possibles altérations de la voie PI3K, de marqueurs de la cascade amyloïde et du DMT2. Le peptide Aβ seul induit peu de changements durables ; le phénotype DMT2 seul est associé à des changements pour quelques protéines-clé, largement en liaison avec le régime cafétéria. Par contre, la majorité des modifications dysfonctionnelles de protéines est observée chez les rats montrant un phénotype de type DMT2 et recevant le peptide Aβ. Ces altérations, similaires à celles rapportées chez des patients atteints de la MA et chez des modèles animaux de la MA, concernent notamment des protéines de la voie PI3K-Akt impliquée dans des fonctions comme l’autophagie et l’inflammation et des marqueurs de la MA. L’altération de ces protéines pourrait contribuer aux déficits mnésiques durables observés et mettre en lumière des mécanismes moléculaires induits par le DMT2 et promouvant un milieu neuronal favorisant le développement d’un stade précoce de la maladie d'Alzheimer. / Following aging, type 2 Diabetes Mellitus (T2DM) is the most important risk factor of developing Alzheimer’s disease (AD). It is a metabolic disorder characterised by hyperglycemia and insulin resistance that develops in middle age and is promoted largely by obesity. In this study, we used a T2DM rat model to assess the potential impact T2DM may have on the development of AD. Rats were fed cafeteria-style diet (CD) coupled with low dose injections of Streptozotocin (STZ)(STZ-CD). We found that STZ-CD treated rats showed classic signs of T2DM and a modest deficit in consolidation of spatial recognition memory. In order to mimic the development of early stage AD, half of the rats were infused with a soluble oligomeric amyloid beta (Aβ), which alone was not sufficient to induce long-lasting memory deficits. Interestingly, the T2DM phenotype exacerbated the memory deficits induced by Aβ infusion by prolonging these deficits. Environmental enrichment during a critical two-week period following infusion of Aβ rescued memory deficits induced by Aβ and/or STZ-CD treatment; however, this was time-limited. Biochemical analyses were conducted mainly in proteins involved in the PI3K-Akt signalling pathway and markers of AD and T2DM in CA1 of the hippocampus. Aβ alone induced few long-lasting changes; T2DM phenotype alone induced some changes that were largely mediated by CD treatment alone; however, the majority of dysfunctional regulation of proteins was observed in rats showing a T2DM phenotype that were infused with Aβ. More importantly, many of these changes are similar to those reported in brains of AD patients or rodent models of the disease; notably key proteins in the PI3K-Akt signaling pathway that mediate functions such as autophagy, inflammation and markers of AD. Dysregulation of these proteins may contribute to the long-lasting memory deficits seen in this model, which may provide evidence of molecular mechanisms induced by T2DM that could promote a dysfunctional neuronal environment favouring the development of early stages of Alzheimer’s disease.