Adenosine A2A Receptor Blockade Modulates Glucocorticoid-Induced Morphological Alterations in Axons, But Not in Dendrites, of Hippocampal Neurons

Detalhes bibliográficos
Autor(a) principal: Pinheiro, Helena
Data de Publicação: 2018
Outros Autores: Gaspar, Rita, Baptista, Filipa, Fontes-Ribeiro, Carlos A., Ambrósio, Francisco, Gomes, Catarina A.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10316/107635
https://doi.org/10.3389/fphar.2018.00219
Resumo: The exposure to supra-physiological levels of glucocorticoids in prenatal life can lead to a long-term impact in brain cytoarchitecture, increasing the susceptibility to neuropsychiatric disorders. Dexamethasone, an exogenous glucocorticoid widely used in pregnant women in risk of preterm delivery, is associated with higher rates of neuropsychiatric conditions throughout life of the descendants. In animal models, prenatal dexamethasone exposure leads to anxious-like behavior and increased susceptibility to depressive-like behavior in adulthood, concomitant with alterations in neuronal morphology in brain regions implicated in the control of emotions and mood. The pharmacologic blockade of the purinergic adenosine A2A receptor, which was previously described as anxiolytic, is also able to modulate neuronal morphology, namely in the hippocampus. Additionally, recent observations point to an interaction between glucocorticoid receptors (GRs) and adenosine A2A receptors. In this work, we explored the impact of dexamethasone on neuronal morphology, and the putative implication of adenosine A2A receptor in the mediation of dexamethasone effects. We report that in vitro hippocampal neurons exposed to dexamethasone (250 nM), in the early phases of development, exhibit a polarized morphology alteration: dendritic atrophy and axonal hypertrophy. While the effect of dexamethasone in the axon is dependent on the activation of adenosine A2A receptor, the effect in the dendrites relies on the activation of GRs, regardless of the activation of adenosine A2A receptor. These results support the hypothesis of the interaction between GRs and adenosine A2A receptors and the potential therapeutic value of modulating adenosine A2A receptors activation in order to prevent glucocorticoid-induced alterations in developing neurons.
id RCAP_615d26166f4f1125e25af05d91c8861c
oai_identifier_str oai:estudogeral.uc.pt:10316/107635
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling Adenosine A2A Receptor Blockade Modulates Glucocorticoid-Induced Morphological Alterations in Axons, But Not in Dendrites, of Hippocampal Neuronsdexamethasoneadenosine A2A receptordevelopmenthippocampal neuronsmorphologyThe exposure to supra-physiological levels of glucocorticoids in prenatal life can lead to a long-term impact in brain cytoarchitecture, increasing the susceptibility to neuropsychiatric disorders. Dexamethasone, an exogenous glucocorticoid widely used in pregnant women in risk of preterm delivery, is associated with higher rates of neuropsychiatric conditions throughout life of the descendants. In animal models, prenatal dexamethasone exposure leads to anxious-like behavior and increased susceptibility to depressive-like behavior in adulthood, concomitant with alterations in neuronal morphology in brain regions implicated in the control of emotions and mood. The pharmacologic blockade of the purinergic adenosine A2A receptor, which was previously described as anxiolytic, is also able to modulate neuronal morphology, namely in the hippocampus. Additionally, recent observations point to an interaction between glucocorticoid receptors (GRs) and adenosine A2A receptors. In this work, we explored the impact of dexamethasone on neuronal morphology, and the putative implication of adenosine A2A receptor in the mediation of dexamethasone effects. We report that in vitro hippocampal neurons exposed to dexamethasone (250 nM), in the early phases of development, exhibit a polarized morphology alteration: dendritic atrophy and axonal hypertrophy. While the effect of dexamethasone in the axon is dependent on the activation of adenosine A2A receptor, the effect in the dendrites relies on the activation of GRs, regardless of the activation of adenosine A2A receptor. These results support the hypothesis of the interaction between GRs and adenosine A2A receptors and the potential therapeutic value of modulating adenosine A2A receptors activation in order to prevent glucocorticoid-induced alterations in developing neurons.Frontiers Media S.A.2018info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107635http://hdl.handle.net/10316/107635https://doi.org/10.3389/fphar.2018.00219eng1663-981229615903Pinheiro, HelenaGaspar, RitaBaptista, FilipaFontes-Ribeiro, Carlos A.Ambrósio, FranciscoGomes, Catarina A.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-25T10:23:33Zoai:estudogeral.uc.pt:10316/107635Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:23:58.015736Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Adenosine A2A Receptor Blockade Modulates Glucocorticoid-Induced Morphological Alterations in Axons, But Not in Dendrites, of Hippocampal Neurons
title Adenosine A2A Receptor Blockade Modulates Glucocorticoid-Induced Morphological Alterations in Axons, But Not in Dendrites, of Hippocampal Neurons
spellingShingle Adenosine A2A Receptor Blockade Modulates Glucocorticoid-Induced Morphological Alterations in Axons, But Not in Dendrites, of Hippocampal Neurons
Pinheiro, Helena
dexamethasone
adenosine A2A receptor
development
hippocampal neurons
morphology
title_short Adenosine A2A Receptor Blockade Modulates Glucocorticoid-Induced Morphological Alterations in Axons, But Not in Dendrites, of Hippocampal Neurons
title_full Adenosine A2A Receptor Blockade Modulates Glucocorticoid-Induced Morphological Alterations in Axons, But Not in Dendrites, of Hippocampal Neurons
title_fullStr Adenosine A2A Receptor Blockade Modulates Glucocorticoid-Induced Morphological Alterations in Axons, But Not in Dendrites, of Hippocampal Neurons
title_full_unstemmed Adenosine A2A Receptor Blockade Modulates Glucocorticoid-Induced Morphological Alterations in Axons, But Not in Dendrites, of Hippocampal Neurons
title_sort Adenosine A2A Receptor Blockade Modulates Glucocorticoid-Induced Morphological Alterations in Axons, But Not in Dendrites, of Hippocampal Neurons
author Pinheiro, Helena
author_facet Pinheiro, Helena
Gaspar, Rita
Baptista, Filipa
Fontes-Ribeiro, Carlos A.
Ambrósio, Francisco
Gomes, Catarina A.
author_role author
author2 Gaspar, Rita
Baptista, Filipa
Fontes-Ribeiro, Carlos A.
Ambrósio, Francisco
Gomes, Catarina A.
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Pinheiro, Helena
Gaspar, Rita
Baptista, Filipa
Fontes-Ribeiro, Carlos A.
Ambrósio, Francisco
Gomes, Catarina A.
dc.subject.por.fl_str_mv dexamethasone
adenosine A2A receptor
development
hippocampal neurons
morphology
topic dexamethasone
adenosine A2A receptor
development
hippocampal neurons
morphology
description The exposure to supra-physiological levels of glucocorticoids in prenatal life can lead to a long-term impact in brain cytoarchitecture, increasing the susceptibility to neuropsychiatric disorders. Dexamethasone, an exogenous glucocorticoid widely used in pregnant women in risk of preterm delivery, is associated with higher rates of neuropsychiatric conditions throughout life of the descendants. In animal models, prenatal dexamethasone exposure leads to anxious-like behavior and increased susceptibility to depressive-like behavior in adulthood, concomitant with alterations in neuronal morphology in brain regions implicated in the control of emotions and mood. The pharmacologic blockade of the purinergic adenosine A2A receptor, which was previously described as anxiolytic, is also able to modulate neuronal morphology, namely in the hippocampus. Additionally, recent observations point to an interaction between glucocorticoid receptors (GRs) and adenosine A2A receptors. In this work, we explored the impact of dexamethasone on neuronal morphology, and the putative implication of adenosine A2A receptor in the mediation of dexamethasone effects. We report that in vitro hippocampal neurons exposed to dexamethasone (250 nM), in the early phases of development, exhibit a polarized morphology alteration: dendritic atrophy and axonal hypertrophy. While the effect of dexamethasone in the axon is dependent on the activation of adenosine A2A receptor, the effect in the dendrites relies on the activation of GRs, regardless of the activation of adenosine A2A receptor. These results support the hypothesis of the interaction between GRs and adenosine A2A receptors and the potential therapeutic value of modulating adenosine A2A receptors activation in order to prevent glucocorticoid-induced alterations in developing neurons.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10316/107635
http://hdl.handle.net/10316/107635
https://doi.org/10.3389/fphar.2018.00219
url http://hdl.handle.net/10316/107635
https://doi.org/10.3389/fphar.2018.00219
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1663-9812
29615903
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
_version_ 1799134125768048640