ROLE OF MENINGEAL MACROPHAGES IN THE REGULATION OF HIPPOCAMPAL FUNCTIONS

In recent years, the characterization of immune cells populating central nervous system (CNS) borders is reshaping our understanding of the neuroimmune interplay. Indeed, leukocyte subpopulations residing in the meninges have been linked to the regulation of neuronal circuits and behavior, acting most likely through the release of soluble factors that directly or indirectly affect neuronal activity. Among meningeal immune cells, macrophages represent the most abundant population, yet their role in the modulation of neurogenesis and neuronal function is unknown. Implementing a specific pharmacological approach to deplete border-associated macrophages (BAMs) allowed us to tackle these aspects. RNA sequencing of hippocampal cells following BAM depletion showed an alteration of neuronal processes. Preliminary behavioral analysis also indicated alteration of cognitive processes upon BAM depletion. To identify the molecular mediators of this neuroimmune axis, we tested the effect of candidate molecules on the differentiation of neurospheres in vitro, and we validated those findings using conditional-knockout mice. Overall, this work provides mechanistic insights into a novel physiological neuroimmune axis. Its relevance in neurodevelopmental and neuroinflammatory contexts will be the matter of future investigations.