Studies on the vascular heterogeneity of the nervous system

• Grant number: 18/25016-0
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2019
• End date: May 31, 2022
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Ricardo Jose Giordano
• Grantee: Ricardo Jose Giordano
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Associated scholarship(s): 19/15113-1 - Studying the brain vascular heterogeneity, BP.TT

Abstract

The concept of vascular heterogeneity is well accepted by the scientific community, playing an essential role in physiological and pathological processes. Since blood vessels are important in organogenesis, differentiation, and morphogenesis of tissues and organs, it becomes interesting to unveil the cerebral vascular diversity, identifying new molecular markers for such important organ. Using in vivo phage display, we show that a new peptide motif that emerged from our combinatorial screening of the vasculature binds selectively to blood vessels in the brain in vivo but not to vessels in other organs. Peptides containing a conserved motif in which amino acids Phenylalanine-Arginine-Tryptophan (Phe-Arg-Trp; FRW) predominate could be visualized by transmission electron microscopy bound to the junctions between endothelial in all areas of the brain, including the optic nerve but not in other barrier containing tissues, such as intestines and testis. Remarkably, peptides containing the motif do not bind to vessels in the retina, implying an important molecular difference between these two vascular barriers. Furthermore, the peptide allows for in vivo imaging, demonstrating that new tools for studying and imaging the brain are likely to emerge from this motif. Here, in this project, we will study the contribution of different components of cellular junctions in to identify the receptor for peptide containing the FRW motif. This is an important step toward understanding the specificity of this motif for the brain vasculature and may contribute for the development of novel therapeutic and diagnostic alternative for patients with disease of the central nervous system. (AU)