Study of neurotoxicity mechanisms of soluble beta-amyloid peptide oligomers in slice cultures of the adult human brain

• Grant number: 20/02569-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2020
• End date: February 28, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Adriano Silva Sebollela
• Grantee: Giovanna Orlovski Nogueira
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The present project proposes the use of organotypic cultures of adult human brain tissue, prepared using tissue obtained from patients undergoing neurosurgical treatments at Hospital das Clinicas in Ribeirão Preto, as a model for studying molecular and cellular changes associated with beta-amyloid peptide oligomers toxicity, and its relationship with Alzheimer's Disease. The slices in culture will be challenged with soluble oligomers of the ²-amyloid peptide (A²Os) to assess its toxicity and the activation pattern of microglial cells. Morphological changes will be evaluated by immunohistochemistry, and so will be the subcellular location of A²Os linked to neurons in the slices, in addition to cell viability by tests such as MTT. This project aims, therefore, to contribute to the understanding of cellular alterations caused by A²Os in an adult human CNS model, in addition to consolidating our ex vivo culture model as the preferred platform for studying neurodegenerative diseases.