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Adenosine A2A receptors blockade attenuates dexamethasone-induced alterations in cultured astrocytes

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Abstract

Anxiety involves abnormal glucocorticoid signalling and altered glia-neuron communication in brain regions processing emotional responses. Adenosine A2A receptor (A2AR) blockade ameliorates mood and memory impairments by preventing synaptic dysfunction and astrogliosis. Since the glucocorticoid dexamethasone (DEX) can mimic early life-stress conditions, leading to anxiety-like behaviours, we now tested if A2AR blockade prevents alterations in the morphology and function of astrocytes exposed to DEX. Cultured astrocytes exposed to DEX exhibited an up-regulation of astrocytic markers (GFAP, connexin-43 and glutamine synthetase), as well as of A2AR. Moreover, DEX enhanced ATP and glutamate release and increased basal astrocytic Ca2+ levels. The selective A2AR antagonist SCH58261 prevented DEX-induced alterations in ATP release and basal Ca2+ levels but did not affect DEX-induced alteration of glutamate release and astrocytic markers. These findings suggest that alterations in astrocytes function, which might contribute to abnormal glucocorticoid brain signalling, are controlled by A2AR, and therefore, reinforce the relevance of A2AR as a potential therapeutic target to manage mood disorders.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

Supported by La Caixa Foundation (HP17/00523), Centro 2020 (CENTRO-01–0145-FEDER-000008:BrainHealth2020 and CENTRO-01–0246-FEDER-000010), and FCT (POCI-01–0145-FEDER-03127, UIDB/04539/2020 and IF/01492/2015). PhD grants of Daniela Madeira (SFRH/BD/139334/2018) and of Liliana Dias (SFRH/BD/147159/2019).

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Authors and Affiliations

  1. CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

    Daniela Madeira, Liliana Dias, Patrícia Santos, Rodrigo A. Cunha, Paula Agostinho & Paula M. Canas

  2. Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Daniela Madeira, Liliana Dias, Rodrigo A. Cunha & Paula Agostinho

Authors
  1. Daniela Madeira
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  2. Liliana Dias
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  3. Patrícia Santos
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  4. Rodrigo A. Cunha
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  5. Paula Agostinho
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  6. Paula M. Canas
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Corresponding authors

Correspondence to Paula Agostinho or Paula M. Canas.

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Ethics approval

This study was approved by the ORBEA_128_2015/04122015 and certified by Direção Geral de Alimentação e Veterinária (DGAV; 0421/000/000/2016 Ref 014,420).

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RAC is a scientific consultant for the Institute for Scientific Information on Coffee. All other authors declare no conflict of interests.

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Madeira, D., Dias, L., Santos, P. et al. Adenosine A2A receptors blockade attenuates dexamethasone-induced alterations in cultured astrocytes. Purinergic Signalling 18, 199–204 (2022). https://doi.org/10.1007/s11302-022-09864-4

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  • DOI: https://doi.org/10.1007/s11302-022-09864-4

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