In vitro modeling of sporadic Alzheimer's disease associated with hyperglycemia

• Grant number: 23/08072-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2023
• End date: December 31, 2023
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marimélia Aparecida Porcionatto
• Grantee: Maria Fernanda Kobayashi Rossi
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 18/12605-8 - Development of brain-on-a-chip microplataforms for in vitro modeling of the central nervous system, AP.TEM

Abstract

With the increase in life expectancy, there is also an increase in the incidence of diseases linked to aging, two of which stand out are Diabetes Mellitus (DM) and Alzheimer's Disease (AD). Although both are complex diseases involving energy metabolism and the other affecting the central nervous system (CNS), the literature has pointed to possible connections between these conditions. Since one of the most well-established complications of diabetes is vascular complications, the blood-brain barrier (BBB) is a potentially affected structure. The integrity of the BBB is fundamental in maintaining the physiology of the CNS, based on the selective exchange of substances with blood circulation. Thus, the main objective of this project is the modeling of an in vitro system of the BBB, aiming to analyze the effects of high glucose, one of the hallmarks of DM, both in the endothelial cells that make up the BBB and in a model of neuronal cells subjected to a microenvironment that mimics AD. For this, endothelial cells derived from human induced pluripotent cells (hiPSC) and SH-SY5Y cells derived from human neuroblastoma, treated with oligomers of ²-amyloid peptide (A²Os), will be used. After the development and standardization of the model, factors such as membrane permeability, oxidative stress, and cell death will be observed. Thus, it is expected that, through the developed model, it will be possible to mimic the hyperglycemia condition and how it can impact the development and progression of AD.