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Region-specific control of microglia by adenosine A2A receptors: uncoupling anxiety and associated cognitive deficits in female rats

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Resumo:Epidemiologic studies have provided compelling evidence that prenatal stress, through excessive maternal glucocorticoids exposure, is associated with psychiatric disorders later in life. We have recently reported that anxiety associated with prenatal exposure to dexamethasone (DEX, a synthetic glucocorticoid) correlates with a gender-specific remodeling of microglia in the medial prefrontal cortex (mPFC), a core brain region in anxiety-related disorders. Gender differences in microglia morphology, the higher prevalence of anxiety in women and the negative impact of anxiety in cognition, led us to specifically evaluate cognitive behavior and associated circuits (namely mPFC-dorsal hippocampus, dHIP), as well as microglia morphology in female rats prenatally exposed to dexamethasone (in utero DEX, iuDEX). We report that iuDEX impaired recognition memory and deteriorated neuronal synchronization between mPFC and dHIP. These functional deficits are paralleled by microglia hyper-ramification in the dHIP and decreased ramification in the mPFC, showing a heterogeneous remodeling of microglia morphology, both postnatally and at adulthood in different brain regions, that differently affect mood and cognition. The chronic blockade of adenosine A2A receptors (A2A R), which are core regulators of microglia morphology and physiology, ameliorated the cognitive deficits, but not the anxiety-like behavior. Notably, A2A R blockade rectified both microglia morphology in the dHIP and the lack of mPFC-dHIP synchronization, further heralding their role in cognitive function.
Autores principais:Duarte, Joana Mendes
Outros Autores:Gaspar, Rita; Caetano, Liliana; Patrício, Patrícia; Cunha, Carina Isabel Soares; Pinheiro, António Maria Restolho Mateus; Alves, Nuno Dinis Lopes Oliveira; Santos, Ana Rita; Ferreira, Samira G.; Sardinha, Vanessa Alexandra Morais; Oliveira, João F.; Fontes-Ribeiro, Carlos; Sousa, Nuno; Cunha, Rodrigo A.; Ambrósio, António F.; Pinto, Luísa; Rodrigues, Ana João; Gomes, Catarina A.
Assunto:A(2A) receptors anxiety cognition gender dimorphism microglia morphology A receptors 2A
Ano:2019
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho

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