Anales RANF

P.76 ADENOSINE A2A RECEPTOR MODULATION OF MICROGLIA MORPHOLOGIC REMODELLING IN EARLY NEURODEVELOPMENT - GENDER BIAS IN PHYSIOLOGY AND PSYCHIATRIC DISORDERS C. Henriques 1 , M. Mateus-Pinheiro 1 , R. Gaspar 1 , J.M. Duarte 1 , H. Pinheiro 1 , F.I. Baptista 1 , P.M. Canas 1 ,R.A. Cunha, A.F. Ambrósio 1 , C.A. Gomes 1 1 . University of Coimbra, Coimbra, Portugal. Sexual differentiation in rodents occurs in the late gestational period, promoting gender asymmetries. Microglia (innate immune cells of the central nervous system) exert important functions from development onwards, fundamentally supported by their highly dynamic cellular processes, in constant expansion and retraction in order to monitor brain homeostasis. We previously described sex differences in microglia morphology in the adult prefrontal cortex (PFC). Prenatal anxiogenic stimulus are associated with anxious-like phenotypes at adulthood, in parallel with a gender-specific morphological remodelling of microglia in the PFC. The chronic blockade of adenosine A2A receptors (A2AR), modulators of microglia morphology, recovered this phenotype only in males. These receptors emerge as potential therapeutic targets in anxiety, due to its ability to modulate microglia. To clarify the organizational role of A2AR in microglia morphological differentiation, we quantitatively characterized microglial processes (number and length) in wild type and A2AR KO mice in the PFC and in the dorsal hippocampus (dHIP) (key brain regions in mood disorders), in both sexes by immunohistochemistry followed by manual 3D reconstruction using Neurolucida software. We observed physiological interregional and sex differences: male microglia were more complex in the dHIP, while female microglia were more complex in the PFC. The genetic deletion of A2AR promoted a hypertrophy of PFC microglia only in females. Concluding, there are microglial subpopulations characterized by regional- and sex- specific morphological asymmetries. The impact of A2AR genetic deletion anticipates an organizational effect of these receptors upon the segregation of microglia subpopulations with sex and regional specificities. Support: Foundation for Science and Technology (FCT), Portugal FCT (PD/BD/114116/2015 and Strategic Project UID/NEU/04539/2013), COMPETE-FEDER (POCI-01-0145-FEDER-007440), Centro 2020 Regional Operational Programme (CENTRO-01-0145-FEDER-000008: BRAINHEALTH 2020).