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Soutenance de thèse le mardi 6 juin 2017

Mardi 6 juin à 14h00 en salle de Conférence de l’IBAIC bâtiment 446 - Rez-de-Chaussée - Université Paris-Sud,
Su Men présente un exposé intitulé
« Type 2 Diabetes Mellitus acts as a risk factor for the development of early stage Alzheimer’s disease »

- Voir le pdf

Jury members :

  • Dr. DAVIS Sabrina, University of Paris-Saclay, Directrice de thèse
  • Dr. FERREIRA Guillaume, University of Bordeaux, Rapporteur
  • Pr. KELLY Aine, University of Dublin, Rapporteur
  • Dr. DAUMAS Stéphanie, University of Sorbonne, Examinateur
  • Pr. TAOUIS Mohammed, University of Paris-Saclay, Examinateur

 

Abstract :
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 AD.

Agenda

  • Mardi 6 juin 14:00-17:00 - Men SU - Institut Neuro-PSI

    Type 2 Diabetes Mellitus acts as a risk factor for the development of early stage Alzheimer’s disease

    Résumé : Soutenance de Thèse
    Sous la direction de Sabrina Davis.
    Équipe : Mécanismes cellulaires et moléculaires de la plasticité et de la mémoire

    Lieu : Salle de Conférences de l'IBAIC - Bâtiment 444, Université de Paris-Sud, Orsay


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