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Anti-inflammatory treatment rescues memory deficits during aging in nfkb1−/− mice

Lookup NU author(s): Edward Fielder, Dr Clare Tweedy, Dr Caroline Wilson, Professor Fiona Oakley, Dr Fiona LeBeau, Dr Joao Passos, Professor Derek Mann, Professor Thomas von Zglinicki, Dr Diana Jurk

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.Chronic inflammation is a common feature of many age-related conditions including neurodegenerative diseases such as Alzheimer's disease. Cellular senescence is a state of irreversible cell-cycle arrest, thought to contribute to neurodegenerative diseases partially via induction of a chronic pro-inflammatory phenotype. In this study, we used a mouse model of genetically enhanced NF-κB activity (nfκb1−/−), characterized by low-grade chronic inflammation and premature aging, to investigate the impact of inflammaging on cognitive decline. We found that during aging, nfkb1−/− mice show an early onset of memory loss, combined with enhanced neuroinflammation and increased frequency of senescent cells in the hippocampus and cerebellum. Electrophysiological measurements in the hippocampus of nfkb1−/− mice in vitro revealed deficits in gamma frequency oscillations, which could explain the decline in memory capacity. Importantly, treatment with the nonsteroidal anti-inflammatory drug (NASID) ibuprofen reduced neuroinflammation and senescent cell burden resulting in significant improvements in cognitive function and gamma frequency oscillations. These data support the hypothesis that chronic inflammation is a causal factor in the cognitive decline observed during aging.


Publication metadata

Author(s): Fielder E, Tweedy C, Wilson C, Oakley F, LeBeau FEN, Passos JF, Mann DA, von Zglinicki T, Jurk D

Publication type: Article

Publication status: Published

Journal: Aging Cell

Year: 2020

Volume: 19

Issue: 10

Print publication date: 01/10/2020

Online publication date: 11/09/2020

Acceptance date: 14/06/2020

Date deposited: 20/11/2020

ISSN (print): 1474-9718

ISSN (electronic): 1474-9726

Publisher: Blackwell Publishing Ltd

URL: https://doi.org/10.1111/acel.13188

DOI: 10.1111/acel.13188

PubMed id: 32915495


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