Aging and Microglial Response following Systemic Stimulation with Escherichia coli in Mice

Inge C. M. Hoogland, Dunja Westhoff, Joo-Yeon Engelen-Lee, Mercedes Valls Seron, Judith H. M. P. Houben-Weerts, David J. van Westerloo, Tom van der Poll, Willem A. van Gool, Diederik van de Beek

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)

Abstract

Systemic infection is an important risk factor for the development cognitive impairment and neurodegeneration in older people. Animal experiments show that systemic challenges with live bacteria cause a neuro-inflammatory response, but the effect of age on this response in these models is unknown. Young (2 months) and middle-aged mice (13-14 months) were intraperitoneally challenged with live Escherichia coli (E. coli) or saline. The mice were sacrificed at 2, 3 and 7 days after inoculation; for all time points, the mice were treated with ceftriaxone (an antimicrobial drug) at 12 and 24 h after inoculation. Microglial response was monitored by immunohistochemical staining with an ionized calcium-binding adaptor molecule 1 (Iba-1) antibody and flow cytometry, and inflammatory response by mRNA expression of pro- and anti-inflammatory mediators. We observed an increased microglial cell number and moderate morphologically activated microglial cells in middle-aged mice, as compared to young mice, after intraperitoneal challenge with live E. coli. Flow cytometry of microglial cells showed higher CD45 and CD11b expressions in middle-aged infected mice compared to young infected mice. The brain expression levels of pro-inflammatory genes were higher in middle-aged than in young infected mice, while middle-aged infected mice had similar expression levels of these genes in the systemic compartment. We conclude that systemic challenge with live bacteria causes an age-dependent neuro-inflammatory and microglial response. Our data show signs of an age-dependent disconnection of the inflammatory transcriptional signature between the brain and the systemic compartment.
Original languageEnglish
Article number279
Pages (from-to)1-22
Number of pages22
JournalCells
Volume10
Issue number2
DOIs
Publication statusPublished - Feb 2021

Keywords

  • Ageing
  • Escherichia coli
  • Microglia
  • Microglial activation
  • Mouse model
  • Neuro-inflammation
  • Systemic infection

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