Cross Talk Between Brain Innate Immunity And Serotonin Signaling Underlies Depressive-like Behavior Induced By Alzheimer's Amyloid-beta Oligomers In Mice

dc.creatorLedo
dc.creatorJose Henrique; Azevedo
dc.creatorEstefania P.; Beckman
dc.creatorDanielle; Ribeiro
dc.creatorFelipe C.; Santos
dc.creatorLuis E.; Razolli
dc.creatorDaniela S.; Kincheski
dc.creatorGrasielle C.; Melo
dc.creatorHelen M.; Bellio
dc.creatorMaria; Teixeira
dc.creatorAntonio L.; Velloso
dc.creatorLicio A.; Foguel
dc.creatorDebora; De Felice
dc.creatorFernanda G.; Ferreira
dc.creatorSergio T.
dc.date2016
dc.datenov
dc.date2017-11-13T13:55:52Z
dc.date2017-11-13T13:55:52Z
dc.date.accessioned2018-03-29T06:09:21Z
dc.date.available2018-03-29T06:09:21Z
dc.identifierJournal Of Neuroscience . Soc Neuroscience , v. 36, p. 12106 - 12116, 2016.
dc.identifier0270-6474
dc.identifierWOS:000391140400005
dc.identifier10.1523/JNEUROSCI.1269-16.2016
dc.identifierhttp://www.jneurosci.org/content/36/48/12106
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/329752
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1366777
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionConsiderable clinical and epidemiological evidence links Alzheimer's disease (AD) and depression. However, the molecular mechanisms underlying this connection are largely unknown. We reported recently that soluble A beta oligomers (A beta Os), toxins that accumulate in AD brains and are thought to instigate synapse damage and memory loss, induce depressive-like behavior in mice. Here, we report that the mechanism underlying this action involves A beta O-induced microglial activation, aberrant TNF-alpha signaling, and decreased brain serotonin levels. Inactivation or ablation of microglia blocked the increase in brain TNF-alpha and abolished depressive-like behavior induced by A beta Os. Significantly, we identified serotonin as a negative regulator of microglial activation. Finally, A beta Os failed to induce depressive-like behavior in Toll-like receptor 4-deficient mice and in mice harboring a nonfunctional TLR4 variant in myeloid cells. Results establish that A beta Os trigger depressive-like behavior via a double impact on brain serotonin levels and microglial activation, unveiling a cross talk between brain innate immunity and serotonergic signaling as a key player in mood alterations in AD.
dc.description36
dc.description48
dc.description12106
dc.description12116
dc.descriptionNational Institute for Translational Neuroscience
dc.descriptionConselho Nacional de Desenvolvimento Cientifico e Tecnologico
dc.descriptionFundacao de Amparo a Pesquisa do Estado do Rio de Janeiro
dc.descriptionHuman Frontiers Science Program
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.languageEnglish
dc.publisherSoc Neuroscience
dc.publisherWashington
dc.relationJournal of Neuroscience
dc.rightsfechado
dc.sourceWOS
dc.subjectAlzheimer's
dc.subjectDepression
dc.subjectInflammation
dc.subjectMicroglia
dc.subjectSerotonin
dc.titleCross Talk Between Brain Innate Immunity And Serotonin Signaling Underlies Depressive-like Behavior Induced By Alzheimer's Amyloid-beta Oligomers In Mice
dc.typeArtículos de revistas


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