UNDERSTANDING THE ROLE OF FATTY ACIDS IN HUMAN MICROGLIA MATURATION DURING NEURODEVELOPMENT

Microglia are brain-resident immune cells essential for homeostasis, playing key roles in brain development. They acquire a distinct homeostatic identity from development to adulthood. Fatty acid binding protein (FABPs) acts as lipid chaperones essential for cellular metabolism, facilitating the intracellular solubilization and noncovalent transport of long-chain polyunsaturated fatty acids (LC-PUFAs). In recent years FABP5 has been associated in modulating microglia and myeloid cell cellular processes, however, how FABP5 influences microglial cellular phenotypes, and functional activity during brain development remains unclear. Our preliminary analysis shows that developing microglia presents a metabolic phenotype switch from transporting LC-PUFAs in early stages to in situ biosynthesis during postnatal maturation, aligned with phenotype signature maturation. To elucidate microglia modulation, this study aims to investigate how FABP5, under basal conditions and in response to LC-PUFAs stimuli, influences microglial maturation from developmental to adult homeostatic state, with a focus on metabolic processing, signaling pathways, and function implication. Human microglial-like cells (iMGLs) at different developmental stages were treated with fatty acids (FA), both in presence and absence of a FABP5 inhibitor, to access their impact on microglial phenotype. We also assessed phagocytic activity by challenging iMGL with E. coli bioparticles or apoptotic cells and performed live imaging to evaluate associated functional changes. We found that FA treatment modulates microglia phenotypes and enhances phagocytic activity over 24 hours. These preliminary findings indicate that iMGL responses vary according to FA type and FABP5 inhibition. In summary, this study provides evidence that LC-PUFAs have demonstrated effect on microglia function and phagocytosis.