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000153985 0247_ $$2ISSN$$a0021-9738
000153985 0247_ $$2ISSN$$a1558-8238
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000153985 041__ $$aEnglish
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000153985 1001_ $$0P:(DE-2719)2812184$$aKeane, Lily$$b0$$eFirst author
000153985 245__ $$amTOR-dependent translation amplifies microglia priming in aging mice
000153985 260__ $$aAnn Arbor, Mich.$$bASCJ$$c2021
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000153985 520__ $$aMicroglia maintain homeostasis in the brain. However, with age, they become primed and respond more strongly to inflammatory stimuli. We show here that microglia from aged mice had upregulated mTOR complex 1 signaling controlling translation, as well as protein levels of inflammatory mediators. Genetic ablation of mTOR signaling showed a dual yet contrasting effect on microglia priming: it caused an NF-κB–dependent upregulation of priming genes at the mRNA level; however, mice displayed reduced cytokine protein levels, diminished microglia activation, and milder sickness behavior. The effect on translation was dependent on reduced phosphorylation of 4EBP1, resulting in decreased binding of eIF4E to eIF4G. Similar changes were present in aged human microglia and in damage-associated microglia, indicating that upregulation of mTOR-dependent translation is an essential aspect of microglia priming in aging and neurodegeneration.
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000153985 650_2 $$2MeSH$$aAging: genetics
000153985 650_2 $$2MeSH$$aAging: metabolism
000153985 650_2 $$2MeSH$$aAnimals
000153985 650_2 $$2MeSH$$aEukaryotic Initiation Factor-4E: genetics
000153985 650_2 $$2MeSH$$aEukaryotic Initiation Factor-4E: metabolism
000153985 650_2 $$2MeSH$$aEukaryotic Initiation Factor-4G: genetics
000153985 650_2 $$2MeSH$$aEukaryotic Initiation Factor-4G: metabolism
000153985 650_2 $$2MeSH$$aHumans
000153985 650_2 $$2MeSH$$aMice
000153985 650_2 $$2MeSH$$aMice, Transgenic
000153985 650_2 $$2MeSH$$aMicroglia: enzymology
000153985 650_2 $$2MeSH$$aNF-kappa B: genetics
000153985 650_2 $$2MeSH$$aNF-kappa B: metabolism
000153985 650_2 $$2MeSH$$aPhosphorylation: genetics
000153985 650_2 $$2MeSH$$aProtein Biosynthesis
000153985 650_2 $$2MeSH$$aSignal Transduction
000153985 650_2 $$2MeSH$$aTOR Serine-Threonine Kinases: genetics
000153985 650_2 $$2MeSH$$aTOR Serine-Threonine Kinases: metabolism
000153985 693__ $$0EXP:(DE-2719)IDAF-20190308$$5EXP:(DE-2719)IDAF-20190308$$eImage and Data Analysis Facility (CRFS-IDAF) / Bonn$$x0
000153985 693__ $$0EXP:(DE-2719)LMF-20190308$$5EXP:(DE-2719)LMF-20190308$$eLight Microscope Facility (CRFS-LMF) / Bonn$$x1
000153985 7001_ $$0P:(DE-2719)2812671$$aAntignano, Ignazio$$b1$$eFirst author
000153985 7001_ $$0P:(DE-2719)9000721$$aRiechers, Sean-Patrick$$b2
000153985 7001_ $$0P:(DE-HGF)0$$aZollinger, Raphael$$b3
000153985 7001_ $$0P:(DE-HGF)0$$aDumas, Anaelle A.$$b4
000153985 7001_ $$0P:(DE-2719)2811777$$aOffermann, Nina$$b5
000153985 7001_ $$0P:(DE-2719)2810557$$aBernis, Maria E.$$b6
000153985 7001_ $$0P:(DE-2719)2812322$$aRuss, Jenny$$b7
000153985 7001_ $$0P:(DE-2719)9000563$$aGraelmann, Frederike$$b8
000153985 7001_ $$0P:(DE-2719)9000662$$aMcCormick, Patrick Neil$$b9
000153985 7001_ $$0P:(DE-2719)2812406$$aEsser, Julia$$b10
000153985 7001_ $$0P:(DE-2719)2812345$$aTejera, Dario$$b11
000153985 7001_ $$0P:(DE-HGF)0$$aNagano, Ai$$b12
000153985 7001_ $$0P:(DE-HGF)0$$aWang, Jun$$b13
000153985 7001_ $$0P:(DE-HGF)0$$aChelala, Claude$$b14
000153985 7001_ $$0P:(DE-2719)2812057$$aBiederbick, Yvonne$$b15
000153985 7001_ $$0P:(DE-2719)2812038$$aHalle, Annett$$b16
000153985 7001_ $$0P:(DE-2719)2811779$$aSalomoni, Paolo$$b17
000153985 7001_ $$0P:(DE-2719)2000008$$aHeneka, Michael T.$$b18
000153985 7001_ $$0P:(DE-2719)2811780$$aCapasso, Melania$$b19$$eLast author
000153985 773__ $$0PERI:(DE-600)2018375-6$$a10.1172/JCI132727$$gVol. 131, no. 1, p. e132727$$n1$$pe132727$$tThe journal of clinical investigation$$v131$$x1558-8238$$y2021
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