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mTOR-dependent translation amplifies microglia priming in aging mice
Lily Keane, Ignazio Antignano, Sean-Patrick Riechers, Raphael Zollinger, Anaelle A. Dumas, Nina Offermann, Maria E. Bernis, Jenny Russ, Frederike Graelmann, Patrick Neil McCormick, Julia Esser, Dario Tejera, Ai Nagano, Jun Wang, Claude Chelala, Yvonne Biederbick, Annett Halle, Paolo Salomoni, Michael T. Heneka, and Melania Capasso
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Published October 15, 2021 - More info
J Clin Invest. 2021;131(20):e155208. https://doi.org/10.1172/JCI155208.
© 2021 American Society for Clinical Investigation
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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.
Authors
Lily Keane, Ignazio Antignano, Sean-Patrick Riechers, Raphael Zollinger, Anaelle A. Dumas, Nina Offermann, Maria E. Bernis, Jenny Russ, Frederike Graelmann, Patrick Neil McCormick, Julia Esser, Dario Tejera, Ai Nagano, Jun Wang, Claude Chelala, Yvonne Biederbick, Annett Halle, Paolo Salomoni, Michael T. Heneka, Melania Capasso
Original citation: J Clin Invest. 2021;131(1):e132727. https://doi.org/10.1172/JCI132727
Citation for this corrigendum: J Clin Invest. 2021;131(20):e155208. https://doi.org/10.1172/JCI155208
During the preparation for this manuscript, the Western blots for p-4EBP1 Thr70 and p-4EBP1 Ser 65 in Figure 6A were inadvertently interchanged. The correct figure part is below.
The authors regret the error.
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ISSN: 0021-9738 (print), 1558-8238 (online)