dc.contributor.author
Batalha, Vania L.
dc.contributor.author
Ferreira, Diana G.
dc.contributor.author
Coelho, Joana E.
dc.contributor.author
Valadas, Jorge S.
dc.contributor.author
Gomes, Rui
dc.contributor.author
Temido-Ferreira, Mariana
dc.contributor.author
Shmidt, Tatian
dc.contributor.author
Buee, Luc
dc.contributor.author
Mueller, Christa E.
dc.contributor.author
Hamdane, Malika
dc.contributor.author
Outeiro, Tiago F.
dc.contributor.author
Bader, Michael
dc.contributor.author
Meijsing, Sebastiaan H.
dc.contributor.author
Sadri-Vakili, Ghazaleh
dc.contributor.author
Blum, David
dc.contributor.author
Lopes, Luisa V.
dc.date.accessioned
2018-06-08T03:20:13Z
dc.date.available
2016-09-15T11:41:41.496Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/14960
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-19148
dc.description.abstract
Caffeine is associated with procognitive effects in humans by counteracting
overactivation of the adenosine A2A receptor (A2AR), which is upregulated in
the human forebrain of aged and Alzheimer’s disease (AD) patients. We have
previously shown that an anti-A2AR therapy reverts age-like memory deficits,
by reestablishment of the hypothalamic-pituitary-adrenal (HPA) axis feedback
and corticosterone circadian levels. These observations suggest that A2AR
over-activation and glucocorticoid dysfunction are key events in age-related
hippocampal deficits; but their direct connection has never been explored. We
now show that inducing A2AR overexpression in an aging-like profile is
sufficient to trigger HPA-axis dysfunction, namely loss of plasmatic
corticosterone circadian oscillation, and promotes reduction of GR hippocampal
levels. The synaptic plasticity and memory deficits triggered by GR in the
hippocampus are amplified by A2AR over-activation and were rescued by anti-
A2AR therapy; finally, we demonstrate that A2AR act on GR nuclear
translocation and GR-dependent transcriptional regulation. We provide the
first demonstration that A2AR is a major regulator of GR function and that
this functional interconnection may be a trigger to age-related memory
deficits. This supports the idea that the procognitive effects of A2AR
antagonists, namely caffeine, on Alzheimer’s and age-related cognitive
impairments may rely on its ability to modulate GR actions.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
The caffeine-binding adenosine A2A receptor induces age-like HPA-axis
dysfunction by targeting glucocorticoid receptor function
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Scientific Reports. - 6 (2016), Artikel Nr. 31493
dcterms.bibliographicCitation.doi
10.1038/srep31493
dcterms.bibliographicCitation.url
http://www.nature.com/articles/srep31493
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000025356
refubium.note.author
Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000006956
dcterms.accessRights.openaire
open access