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

Edward Fielder, Clare Tweedy, Caroline Wilson, Fiona Oakley, Fiona E.N. LeBeau, João F. Passos, Derek A. Mann, Thomas von Zglinicki, Diana Jurk

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere13188
JournalAging Cell
Volume19
Issue number10
DOIs
StatePublished - Oct 1 2020

Keywords

  • aging
  • cognitive decline
  • hippocampus
  • memory
  • neuroinflammation
  • senescence

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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