ROLE OF MENINGEAL MACROPHAGES IN DEVELOPMENTAL NEUROGENESIS AND MEMORY FUNCTION

The meninges are a protective and nutritious tissue that surrounds the central nervous system and supports the brain. Recent data, including from our team, have revealed that the meninges contain a myriad of immune cells, such as Border Associated Macrophages (BAMs). An analysis of the transcriptome of meningeal macrophages at different stages of life suggests their involvement in developmental features during the neonatal period, gradually replaced by a role in protecting the central nervous system against infections. To address this hypothesis, we are developing novel chemical and genetic models to deplete BAMs in neonatal mice and measure the impact of this depletion on hippocampal neurogenesis. We are also investigating long-term consequences of this depletion on mice behavior (contextual memory) and neuroactivation. Thanks to mass spectrometry of the cerebrospinal fluid and multi-RNA sequencing analyses of meningeal and brain tissues associated with computed cell-cell communication algorithms, we are investigating in-vivo and in-vitro a panel of ligands that could support communication between BAMs and the brain. This work could ultimately uncover the involvement of BAMs in brain development and cognitive functions, thereby paving the way for a potential role of these cells in physiological and pathological condition (i.e., onset of neurodevelopmental disorders.)