Electronic Poster | Session 1

006 – Regional distribution, density, and morphology of the peripheral myeloid cells invading the murine brain during normal postnatal development

Micaël Carrier (1) – Marie-Ève Robert (1) – Julie C. Savage (1) – Frederic Geissmann (2) – Marie-Ève Tremblay (1)
Axe neurosciences, Centre de recherche du CHU de Québec-Université Laval, Faculté de médecine, Université Laval, Québec, Canada (1) – Immunology Program and Ludwig Center at Memorial Sloan Kettering Cancer Center, Memorial Sloan Kettering Cancer Center, New-York, United States (2)

Microglia are the resident immune cells of the brain that exclusively derive from the embryonic yolk sac. During trauma or disease, bone marrow-derived cells (BMDC) can also invade the brain, infiltrating through the blood-brain barrier (BBB), to accomplish neuroinflammatory roles. We have described at the ultrastructural level a new phenotype of brain myeloid cells that is highly prevalent upon chronic stress, aging, and neurodegenerative disease. Recently, we also found these cells to be abundant during normal development. These ‘dark microglia’ are tightly associated with blood vessels. They also interact extensively with synapses, suggesting their possible implication in the remodeling of neuronal circuits. To study this phenotype in the context of homeostatic development and determine their origin from the bone marrow or embryonic yolk sac, this study was conducted using Flt3creRFPlox mouse model in which BMDC are selectively labelled, without radiation or chemotherapy that can affect the BBB permeability. The animals were sacrificed under steady-state conditions at different postnatal ages from birth until adulthood. Serial sections providing a non-biased representation of the brain were then immunostained for the microglia/macrophage marker IBA1 and imaged with a slide scanner to analyze the regional distribution, density, and morphology of the FLT3/IBA positive cells across development. 3D electron microscopy with immunostaining (array tomography technology) experiments are now underway to determine the origin of dark microglia.