Home > Publications Database > mTOR-dependent translation amplifies microglia priming in aging mice > print

001     153985
005     20240529143839.0
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024 7 _ |a 10.1172/JCI132727
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024 7 _ |a 1558-8238
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037 _ _ |a DZNE-2021-00002
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Keane, Lily
|0 P:(DE-2719)2812184
|b 0
|e First author
245 _ _ |a mTOR-dependent translation amplifies microglia priming in aging mice
260 _ _ |a Ann Arbor, Mich.
|c 2021
|b ASCJ
336 7 _ |a article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a Microglia 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.
536 _ _ |a 351 - Brain Function (POF4-351)
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588 _ _ |a Dataset connected to CrossRef
650 _ 2 |a Aging: genetics
|2 MeSH
650 _ 2 |a Aging: metabolism
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Eukaryotic Initiation Factor-4E: genetics
|2 MeSH
650 _ 2 |a Eukaryotic Initiation Factor-4E: metabolism
|2 MeSH
650 _ 2 |a Eukaryotic Initiation Factor-4G: genetics
|2 MeSH
650 _ 2 |a Eukaryotic Initiation Factor-4G: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
650 _ 2 |a Microglia: enzymology
|2 MeSH
650 _ 2 |a NF-kappa B: genetics
|2 MeSH
650 _ 2 |a NF-kappa B: metabolism
|2 MeSH
650 _ 2 |a Phosphorylation: genetics
|2 MeSH
650 _ 2 |a Protein Biosynthesis
|2 MeSH
650 _ 2 |a Signal Transduction
|2 MeSH
650 _ 2 |a TOR Serine-Threonine Kinases: genetics
|2 MeSH
650 _ 2 |a TOR Serine-Threonine Kinases: metabolism
|2 MeSH
693 _ _ |0 EXP:(DE-2719)IDAF-20190308
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|e Image and Data Analysis Facility (CRFS-IDAF) / Bonn
|x 0
693 _ _ |0 EXP:(DE-2719)LMF-20190308
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700 1 _ |a Antignano, Ignazio
|0 P:(DE-2719)2812671
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|e First author
700 1 _ |a Riechers, Sean-Patrick
|0 P:(DE-2719)9000721
|b 2
700 1 _ |a Zollinger, Raphael
|0 P:(DE-HGF)0
|b 3
700 1 _ |a Dumas, Anaelle A.
|0 P:(DE-HGF)0
|b 4
700 1 _ |a Offermann, Nina
|0 P:(DE-2719)2811777
|b 5
700 1 _ |a Bernis, Maria E.
|0 P:(DE-2719)2810557
|b 6
700 1 _ |a Russ, Jenny
|0 P:(DE-2719)2812322
|b 7
700 1 _ |a Graelmann, Frederike
|0 P:(DE-2719)9000563
|b 8
700 1 _ |a McCormick, Patrick Neil
|0 P:(DE-2719)9000662
|b 9
700 1 _ |a Esser, Julia
|0 P:(DE-2719)2812406
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700 1 _ |a Tejera, Dario
|0 P:(DE-2719)2812345
|b 11
700 1 _ |a Nagano, Ai
|0 P:(DE-HGF)0
|b 12
700 1 _ |a Wang, Jun
|0 P:(DE-HGF)0
|b 13
700 1 _ |a Chelala, Claude
|0 P:(DE-HGF)0
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700 1 _ |a Biederbick, Yvonne
|0 P:(DE-2719)2812057
|b 15
700 1 _ |a Halle, Annett
|0 P:(DE-2719)2812038
|b 16
700 1 _ |a Salomoni, Paolo
|0 P:(DE-2719)2811779
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700 1 _ |a Heneka, Michael T.
|0 P:(DE-2719)2000008
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700 1 _ |a Capasso, Melania
|0 P:(DE-2719)2811780
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|e Last author
773 _ _ |a 10.1172/JCI132727
|g Vol. 131, no. 1, p. e132727
|0 PERI:(DE-600)2018375-6
|n 1
|p e132727
|t The journal of clinical investigation
|v 131
|y 2021
|x 1558-8238
856 4 _ |u https://pub.dzne.de/record/153985/files/DZNE-2021-00002_Restricted.pdf
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