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Caffeine reverts memory but not mood impairment in a depression-prone mouse strain with up-regulated Adenosine A(2A) receptor in hippocampal glutamate synapses

2017-03Journal article Restricted access
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dc.contributor.authorMachado, Nuno J.
dc.contributor.authorSimoes, Ana Patricia
dc.contributor.authorSilva, Henrique B.
dc.contributor.authorArdais, Ana Paula
dc.contributor.authorKaster, Manuella P.
dc.contributor.authorGarcao, Pedro
dc.contributor.authorRodrigues, Diana I.
dc.contributor.authorPochmann, Daniela
dc.contributor.authorSantos, Ana Isabel
dc.contributor.authorAraújo, Inês
dc.contributor.authorPorciuncula, Lisiane O.
dc.contributor.authorTome, Angelo R.
dc.contributor.authorKofalvi, Attila
dc.contributor.authorVaugeois, Jean-Marie
dc.contributor.authorAgostinho, Paula
dc.contributor.authorEl Yacoubi, Malika
dc.contributor.authorCunha, Rodrigo A.
dc.contributor.authorGomes, Catarina A.
dc.date.accessioned2019-11-20T15:07:45Z
dc.date.available2019-11-20T15:07:45Z
dc.date.issued2017-03
dc.description.abstractCaffeine prophylactically prevents mood and memory impairments through adenosine A(2A) receptor (A(2A)R) antagonism. A(2A)R antagonists also therapeutically revert mood and memory impairments, but it is not known if caffeine is also therapeutically or only prophylactically effective. Since depression is accompanied by mood and memory alterations, we now explored if chronic (4 weeks) caffeine consumption (0.3 g/L) reverts mood and memory impairment in helpless mice (HM, 12 weeks old), a bred-based model of depression. HM displayed higher immobility in the tail suspension and forced swimming tests, greater anxiety in the elevated plus maze, and poorer memory performance (modified Y-maze and object recognition). HM also had reduced density of synaptic (synaptophysin, SNAP-25), namely, glutamatergic (vGluT1; -22 +/- 7 %) and GABAergic (vGAT; -23 +/- 8 %) markers in the hippocampus. HM displayed higher A(2A)R density (72 +/- 6 %) in hippocampal synapses, an enhanced facilitation of hippocampal glutamate release by the A(2A)R agonist, CGS21680 (30 nM), and a larger LTP amplitude (54 +/- 8 % vs. 21 +/- 5 % in controls) that was restored to control levels (30 +/- 10 %) by the A(2A)R antagonist, SCH58261 (50 nM). Notably, caffeine intake reverted memory deficits and reverted the loss of hippocampal synaptic markers but did not affect helpless or anxiety behavior. These results reinforce the validity of HM as an animal model of depression by showing that they also display reference memory deficits. Furthermore, caffeine intake selectively reverted memory but not mood deficits displayed by HM, which are associated with an increased density and functional impact of hippocampal A(2A)R controlling synaptic glutamatergic function.
dc.description.sponsorshipNARSAD
dc.description.sponsorshipDARPA [09-68-ESR-FP-010]
dc.description.sponsorshipFundacao para a Ciencia e para a Tecnologia [PTDC/SAU-NEU/122254/2010, PEst-C/SAU/LA0001/2013-2014]
dc.description.sponsorshipQREN [CENTRO-07-ST24-FEDER-002006]
dc.description.sponsorshipprogram Egide-Pessoa
dc.description.sponsorshipCAPES FCT (Ciencia sem Fronteiras)
dc.identifier.doi10.1007/s12035-016-9774-9
dc.identifier.issn0893-7648
dc.identifier.issn1559-1182
dc.identifier.urihttp://hdl.handle.net/10400.1/13201
dc.language.isoeng
dc.peerreviewedyes
dc.publisherHumana Press Inc
dc.subjectLong-term potentiation
dc.subjectBeta-amyloid peptides
dc.subjectCognitive impairment
dc.subjectSynaptic plasticity
dc.subjectAlzheimers-disease
dc.subjectMajor depression
dc.subjectRat hippocampus
dc.subjectMice
dc.subjectStress
dc.subjectBrain
dc.titleCaffeine reverts memory but not mood impairment in a depression-prone mouse strain with up-regulated Adenosine A(2A) receptor in hippocampal glutamate synapses
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/COMPETE/PTDC%2FSAU-NSC%2F122254%2F2010/PT
oaire.citation.endPage1563
oaire.citation.issue2
oaire.citation.startPage1552
oaire.citation.titleMolecular Neurobiology
oaire.citation.volume54
oaire.fundingStreamCOMPETE
person.familyNamePombinho de Araújo
person.givenNameInês Maria
person.identifierF-4703-2012
person.identifier.ciencia-idD11F-D4CA-2947
person.identifier.orcid0000-0002-2438-0111
person.identifier.scopus-author-id56271084100
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccess
rcaap.typearticle
relation.isAuthorOfPublication1d0c21f4-0f4b-4589-8412-fe1079419774
relation.isAuthorOfPublication.latestForDiscovery1d0c21f4-0f4b-4589-8412-fe1079419774
relation.isProjectOfPublicationc15ea93b-ee60-48b5-8fbc-25436905e845
relation.isProjectOfPublication.latestForDiscoveryc15ea93b-ee60-48b5-8fbc-25436905e845

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