Journal Article

DZNE-2021-00002

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png mTOR-dependent translation amplifies microglia priming in aging mice

Keane, L. (First author)DZNE* ; Antignano, I. (First author)DZNE* ; Riechers, S.-P.DZNE* ; Zollinger, R. ; Dumas, A. A. ; Offermann, N.DZNE* ; Bernis, M. E.DZNE* ; Russ, J.DZNE* ; Graelmann, F.DZNE* ; McCormick, P. N.DZNE* ; Esser, J.DZNE* ; Tejera, D.DZNE* ; Nagano, A. ; Wang, J. ; Chelala, C. ; Biederbick, Y.DZNE* ; Halle, A.DZNE* ; Salomoni, P.DZNE* ; Heneka, M. T.DZNE* ; Capasso, M. (Last author)DZNE*

2021
ASCJ Ann Arbor, Mich.

This record in other databases:    

Please use a persistent id in citations: doi:10.1172/JCI132727

Abstract: 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.

Keyword(s): Aging: genetics (MeSH) ; Aging: metabolism (MeSH) ; Animals (MeSH) ; Eukaryotic Initiation Factor-4E: genetics (MeSH) ; Eukaryotic Initiation Factor-4E: metabolism (MeSH) ; Eukaryotic Initiation Factor-4G: genetics (MeSH) ; Eukaryotic Initiation Factor-4G: metabolism (MeSH) ; Humans (MeSH) ; Mice (MeSH) ; Mice, Transgenic (MeSH) ; Microglia: enzymology (MeSH) ; NF-kappa B: genetics (MeSH) ; NF-kappa B: metabolism (MeSH) ; Phosphorylation: genetics (MeSH) ; Protein Biosynthesis (MeSH) ; Signal Transduction (MeSH) ; TOR Serine-Threonine Kinases: genetics (MeSH) ; TOR Serine-Threonine Kinases: metabolism (MeSH)

---

Contributing Institute(s):

1. Immune Regulation (AG Capasso)
2. Neuroinflammation, Biomarker (AG Heneka ; AG Heneka)
3. Nuclear Function in CNS Pathophysiology (AG Salomoni)
4. Microglia and Neuroinflammation (AG Halle)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)
3. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Experiment(s):

1. Image and Data Analysis Facility (CRFS-IDAF) / Bonn
2. Light Microscope Facility (CRFS-LMF) / Bonn

Appears in the scientific report 2021

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---

---

Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Journal Article (Erratum/Correction) Keane, L. (First author)DZNE* ; Antignano, I.DZNE* ; Riechers, S.-P.DZNE* ; Zollinger, R. ; Dumas, A. A. ; Offermann, N.DZNE* ; Bernis, M. E.DZNE* ; Russ, J.DZNE* ; Graelmann, F.DZNE* ; McCormick, P. N.DZNE* ; Esser, J.DZNE* ; Tejera, D.DZNE* ; Nagano, A. ; Wang, J. ; Chelala, C. ; Biederbick, Y.DZNE* ; Halle, A.DZNE* ; Salomoni, P.DZNE* ; Heneka, M. T.DZNE* ; Capasso, M. (Last author)DZNE*
Corrigendum: mTOR-dependent translation amplifies microglia priming in aging mice.
The journal of clinical investigation 131(20), e155208 (2021) [10.1172/JCI155208]2021   Files  Fulltext Fulltext by Pubmed Central BibTeX | EndNote: XML, Text | RIS

---