Aging and Microglial Response following Systemic Stimulation with <i>Escherichia coli</i> in Mice
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. Y...
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MDPI AG
2021-01-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Inge C.M. Hoogland |
| collection | DOAJ |
| description | 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 <i>Escherichia coli</i> (<i>E. coli</i>) 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 <i>E. coli</i>. 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. |
| first_indexed | 2024-03-09T06:21:23Z |
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| language | English |
| last_indexed | 2024-03-09T06:21:23Z |
| publishDate | 2021-01-01 |
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| series | Cells |
| spelling | doaj.art-f35ea60cceef4810827047b0630fb17a2023-12-03T11:46:48ZengMDPI AGCells2073-44092021-01-0110227910.3390/cells10020279Aging and Microglial Response following Systemic Stimulation with <i>Escherichia coli</i> in MiceInge C.M. Hoogland0Dunja Westhoff1Joo-Yeon Engelen-Lee2Mercedes Valls Seron3Judith H.M.P. Houben-Weerts4David J. van Westerloo5Tom van der Poll6Willem A. van Gool7Diederik van de Beek8Department of Neurology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9, 1105 AZ Amsterdam, The NetherlandsDepartment of Neurology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9, 1105 AZ Amsterdam, The NetherlandsDepartment of Neurology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9, 1105 AZ Amsterdam, The NetherlandsDepartment of Neurology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9, 1105 AZ Amsterdam, The NetherlandsDepartment of Neurology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9, 1105 AZ Amsterdam, The NetherlandsIntensive Care Medicine, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsCentre for Experimental and Molecular Medicine, University of Amsterdam, Amsterdam UMC, Amsterdam Infection and Immunity Institute, Meibergdreef 5, 1105 AZ Amsterdam, The NetherlandsDepartment of Neurology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9, 1105 AZ Amsterdam, The NetherlandsDepartment of Neurology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9, 1105 AZ Amsterdam, The NetherlandsSystemic 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 <i>Escherichia coli</i> (<i>E. coli</i>) 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 <i>E. coli</i>. 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.https://www.mdpi.com/2073-4409/10/2/279microgliamicroglial activationsystemic infection<i>Escherichia coli</i>neuro-inflammationageing |
| spellingShingle | 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 Aging and Microglial Response following Systemic Stimulation with <i>Escherichia coli</i> in Mice Cells microglia microglial activation systemic infection <i>Escherichia coli</i> neuro-inflammation ageing |
| title | Aging and Microglial Response following Systemic Stimulation with <i>Escherichia coli</i> in Mice |
| title_full | Aging and Microglial Response following Systemic Stimulation with <i>Escherichia coli</i> in Mice |
| title_fullStr | Aging and Microglial Response following Systemic Stimulation with <i>Escherichia coli</i> in Mice |
| title_full_unstemmed | Aging and Microglial Response following Systemic Stimulation with <i>Escherichia coli</i> in Mice |
| title_short | Aging and Microglial Response following Systemic Stimulation with <i>Escherichia coli</i> in Mice |
| title_sort | aging and microglial response following systemic stimulation with i escherichia coli i in mice |
| topic | microglia microglial activation systemic infection <i>Escherichia coli</i> neuro-inflammation ageing |
| url | https://www.mdpi.com/2073-4409/10/2/279 |
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