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Integrative analysis of global gene expression identifies opposite patterns of reactive astrogliosis in aged human prefrontal cortex

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dc.creatorPayan-Gomez, Cesar
dc.creatorRodríguez, Diegospa
dc.creatorAmador Muñoz, Diana Patriciaspa
dc.creatorRamírez Clavijo, Sandra Rocío
dc.date.accessioned2020-05-26T00:03:33Z
dc.date.available2020-05-26T00:03:33Z
dc.date.created2018spa
dc.description.abstractThe prefrontal cortex (PFC) is one of the brain regions with more prominent changes in human aging. The molecular processes related to the cognitive decline and mood changes during aging are not completely understood. To improve our knowledge, we integrated transcriptomic data of four studies of human PFC from elderly people (58–80 years old) compared with younger people (20–40 years old) using a meta-analytic approximation combined with molecular signature analysis. We identified 1817 differentially expressed genes, 561 up-regulated and 1256 down-regulated. Pathway analysis revealed down-regulation of synaptic genes with conservation of gene expression of other neuronal regions. Additionally, we identified up-regulation of markers of astrogliosis with transcriptomic signature compatible with A1 neurotoxic astrocytes and A2 neuroprotective astrocytes. Response to interferon is related to A1 astrocytes and the A2 phenotype is mediated in aging by activation of sonic hedgehog (SHH) pathway and up-regulation of metallothioneins I and genes of the family ERM (ezrin, radixin, and moesin). The main conclusions of our study are the confirmation of a global dysfunction of the synapses in the aged PFC and the evidence of opposite phenotypes of astrogliosis in the aging brain, which we report for the first time in the present article. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.3390/brainsci8120227
dc.identifier.issn20763425
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/23603
dc.language.isoengspa
dc.publisherMDPI AGspa
dc.relation.citationIssueNo. 12
dc.relation.citationTitleBrain Sciences
dc.relation.citationVolumeVol. 8
dc.relation.ispartofBrain Sciences, ISSN:20763425, Vol.8, No.12 (2018)spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85070198338&doi=10.3390%2fbrainsci8120227&partnerID=40&md5=37576ea462ceef64c90ebb1db3b899cdspa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subject.keyword4 aminobutyric acidspa
dc.subject.keywordAlpha interferonspa
dc.subject.keywordBeta interferonspa
dc.subject.keywordCadmiumspa
dc.subject.keywordCell proteinspa
dc.subject.keywordCyclic gmpspa
dc.subject.keywordEzrinspa
dc.subject.keywordGlutamic acidspa
dc.subject.keywordInterferonspa
dc.subject.keywordMetallothionein ispa
dc.subject.keywordMoesinspa
dc.subject.keywordOxytocinspa
dc.subject.keywordRadixinspa
dc.subject.keywordSonic hedgehog proteinspa
dc.subject.keywordTranscription factor gli1spa
dc.subject.keywordTranscriptional activator gli3spa
dc.subject.keywordTransient receptor potential channelspa
dc.subject.keywordZinc finger protein gli2spa
dc.subject.keywordAdultspa
dc.subject.keywordAgedspa
dc.subject.keywordAgingspa
dc.subject.keywordArticlespa
dc.subject.keywordAstrocytespa
dc.subject.keywordAstrocytosisspa
dc.subject.keywordComparative studyspa
dc.subject.keywordDown regulationspa
dc.subject.keywordGene expressionspa
dc.subject.keywordGene expression profilingspa
dc.subject.keywordGenetic analysisspa
dc.subject.keywordHumanspa
dc.subject.keywordMeta analysisspa
dc.subject.keywordMolecular biologyspa
dc.subject.keywordNeuroprotectionspa
dc.subject.keywordPhenotypic variationspa
dc.subject.keywordPrefrontal cortexspa
dc.subject.keywordTranscriptomicsspa
dc.subject.keywordUpregulationspa
dc.subject.keywordMeta-analysis of transcriptomicspa
dc.subject.keywordPrefrontal cortex agingspa
dc.subject.keywordReactive astrogliosisspa
dc.subject.keywordSynapsis agingspa
dc.titleIntegrative analysis of global gene expression identifies opposite patterns of reactive astrogliosis in aged human prefrontal cortexspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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