High-resolution imaging of human brain slice cultures challenged with A² oligomers

• Grant number: 24/10164-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: November 01, 2024
• End date: April 30, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Adriano Silva Sebollela
• Grantee: Giovanna Orlovski Nogueira
• Supervisor: Juan Alberto Varela
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of St Andrews, Scotland
• Associated to the scholarship: 22/12904-0 - Identification of molecular mechanisms associated with binding of soluble ²-amyloid peptide oligomers in adult human neural tissue slices, BP.DD

Abstract

Alzheimer's disease (AD) is clinically characterized by progressive memory loss followed by deficits in other cognitive functions, resulting from neuronal damage accumulated over the years and triggered mainly by the binding of soluble oligomers of the amyloid-ß peptide (AßOs). AßOs are associated with neurotoxicity in AD models, including altered gene expression, synaptic loss, production of reactive oxygen species, and changes in synaptic plasticity. In my Ph.D. project, we proposed using slice cultures of adult human brain tissue as a tool to dissect molecular events underlying AßOs attack. Analyzes performed to date indicate that AßOs can bind to adult human brain slices in a cell-associated manner, especially neurons, and induce the release of pro-inflammatory cytokines without reducing cell viability. These results indicate that AßOs induce a pro-inflammatory response in adult human nerve cells in a context of preserved brain tissue, providing an opportunity to investigate the molecular mechanisms associated with the binding of AßOs to neurons. Therefore, we plan to use high-resolution imaging techniques to detail this interaction through an internship with Prof. Varela, which will allow training in high-resolution imaging techniques. The knowledge will be disseminated among colleagues in Prof. Sebollela's laboratory and in the postgraduate program, enhancing collaborations on projects in Brazil and South America.