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Type: Artigo
Title: Cross Talk Between Brain Innate Immunity And Serotonin Signaling Underlies Depressive-like Behavior Induced By Alzheimer's Amyloid-beta Oligomers In Mice
Author: Ledo
Jose Henrique; Azevedo
Estefania P.; Beckman
Danielle; Ribeiro
Felipe C.; Santos
Luis E.; Razolli
Daniela S.; Kincheski
Grasielle C.; Melo
Helen M.; Bellio
Maria; Teixeira
Antonio L.; Velloso
Licio A.; Foguel
Debora; De Felice
Fernanda G.; Ferreira
Sergio T.
Abstract: Considerable 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.
Subject: Alzheimer's
Editor: Soc Neuroscience
Rights: fechado
Identifier DOI: 10.1523/JNEUROSCI.1269-16.2016
Date Issue: 2016
Appears in Collections:Unicamp - Artigos e Outros Documentos

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