Contribution of lipotoxicity in the development of cognitive deficit in Diabetes mellitus Type 2 (T2D)

• Grant number: 18/26013-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2020
• End date: November 30, 2023
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Ubiratan Fabres Machado
• Grantee: Rafael Junges Moreira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/15603-0 - Unraveling mechanisms of glycemic control and chronic complications of Diabetes mellitus: contributions to human health, AP.TEM

Abstract

Diabetes mellitus (DM) and its chronic complications are the major public health problems, making it essential to improve measures to improve glycemic control and reduce the incidence of complications such as dyslipidemia. They are targets of the development of complications, addressed in the present proposal the brain (Alzheimer's Disease, DM3), more precisely the cortex. This proposal has as general objective to expose the molecular mechanisms related to the development of complications in patients with DM2 in the cortex, and its possible relation with lipotoxicity. Thus, in mice with DM2 treated or not with statin, lipid changes occurring in plasma and brain tissue, degree of cognitive activity, and expression of proteins that participate in this pathophysiology as glucose transporters and markers of neuronal degeneration will be investigated. In addition, lipotoxicity will be investigated in cultured neurons. In order to reach this objective, the most varied methodologies will be used: cognitive evaluation through the tests of inhibitory avoidance and the aquatic labyrinth of Morris, culture of neurons SHSY5Y; techniques for evaluation of gene and protein expression (RT-qPCR, Western blotting and ELISA); evaluation of lipids by gas chromatography; and large-scale analysis of the cerebral and neuronal (lipidomic) lipid profile. It is expected to gain a better understanding of how lipid changes in the cerebral cortex may contribute to the development of DM3, and present possible prevention/treatment alternatives. The present study intends to aggregate knowledge that enriches the knowledge of the area with a significant contribution to the health of patients with DM2. (AU)