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Microglia cytoarchitecture in the brain of adenosine A 2A receptor knockout mice: Brain region and sex specificities
Author(s) -
Simões-Henriques Carla,
MateusPinheiro Miguel,
Gaspar Rita,
Pinheiro Helena,
Mendes Duarte Joana,
Baptista Filipa I.,
Canas Paula M.,
Fontes-Ribeiro Carlos Alberto,
Cunha Rodrigo A.,
Ambrósio António F.,
Gomes Catarina A.
Publication year - 2020
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.14561
Subject(s) - microglia , adenosine a2a receptor , prefrontal cortex , neuroscience , knockout mouse , hippocampus , neuroplasticity , psychology , biology , cytoarchitecture , receptor , adenosine receptor , cognition , immunology , inflammation , agonist , genetics
Microglia cells exert a critical role in brain development, mainly supported by their immune functions, which predicts an impact on the genesis of psychiatric disorders. In fact, microglia stress during gestation is, for instance, associated with chronic anxiety and cognitive deficits accompanied by long‐lasting, region‐ and sex‐specific changes in microglia morphology. We recently reported that the pattern of microglia morphologic plasticity, which is sex‐determined, impacts on anxious‐like behaviour and cognition. We also reported that the pharmacologic blockade of adenosine A 2A receptors (A 2 A R ) is able to reshape microglia morphology, in a sex‐specific manner and with behavioural sequelae. In order to better understand the role of A 2 A R in the sex differentiation of microglia, we now compared their morphology in wild‐type and A 2 A R knockout male and female C57 BL /6 mice in two cardinal brain regions implicated in anxiety‐like behaviour and cognition, the prefrontal cortex ( PFC ) and the dorsal hippocampus ( dHIP ). We report interregional differences between PFC and dHIP in a sex‐specific manner: while males presented more complex microglia in the dHIP , microglia from females had a more complex morphology in the PFC . Surprisingly, the genetic deletion of A 2 A R did not alter these sex differences, but promoted the exclusive remodelling (increase in complexity) in PFC microglia from females. These findings further support the existence of a heterogeneous microglial network, distinct between sexes and brain regions, and help characterizing the role of A 2 A R in the sex‐ and brain region‐specific morphologic differentiation of microglia.