Aging and microglial response following systemic stimulation with escherichia coli in mice

Hoogland, I.C.M.; Westhoff, D.; Engelen-Lee, J.Y.; Seron, M.V.; Houben-Weerts, J.H.M.P.; Westerloo, D.J. van; ... ; Beek, D. van de (2021)

Article / Letter to editor

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.

• microglia
• microglial activation
• systemic infection
• Escherichia coli
• neuro-inflammation
• ageing
• mouse model

• All authors: Hoogland, I.C.M.; Westhoff, D.; Engelen-Lee, J.Y.; Seron, M.V.; Houben-Weerts, J.H.M.P.; Westerloo, D.J. van; Poll, T. van der; Gool, W.A. van; Beek, D. van de
• Date: 2021-02-01
• Journal: Cells
• Volume: 10
• Issue: 2
• DOI: doi:10.3390/cells10020279
• Link: https://www.mdpi.com/2073-4409/10/2/279/pdf