Microglial cell response in α7 nicotinic acetylcholine receptor-deficient mice after systemic infection with Escherichia coli.

Abstract

BACKGROUND:

Development of neurodegeneration in older people has been associated with microglial cell activation triggered by systemic infection. We hypothesize that α7 nicotinic acetylcholine receptor (α7nAChR) plays an important role in regulation of this process.

METHODS:

8- to 10-week-old male wild-type (WT) and α7nAChR knock-out (α7nAChR-/-) mice were intraperitoneally inoculated with live Escherichia (E.) coli or saline. After inoculation, all mice were treated with ceftriaxone (an antimicrobial drug) at 12 and 24 h and killed at 2 or 3 days. The microglial response was characterized by immunohistochemical staining with an ionized calcium-binding adaptor molecule 1 (Iba-1) antibody and flow cytometry. To quantify inflammatory response, mRNA expression of pro- and anti-inflammatory mediators was measured in brain and spleen.

RESULTS:

We observed no differences in Iba-1 positive cell number or morphology and flow cytometry (CD11b, CD45 and CD14) of microglial cells between WT and α7nAChR-/- mice after systemic infection. Infected α7nAChR-/- mice showed significantly higher mRNA expression in brain for tumor necrosis factor alpha (TNF-α) at day 2 and 3, interleukin 6 (IL-6) at day 2 and monocyte chemotactic protein 1 (MCP-1) and suppressor of cytokine signaling 1 (SOCS1) at day 3, there was significantly lower mRNA expression in brain for mitogen-activated protein kinase 1 (MAPK1) at day 2 and 3, high-mobility group 1 (HMGB-1) and CD11b at day 2, and deubiquitinase protein A20 (A20) at day 3 compared to infected WT mice.

INTERPRETATION:

Loss of function of α7nAChR during systemic infection led to an increased expression of TNF-α and IL-6 in brain after systemic infection with E. coli, but not to distinct differences in microglial cell number or morphological activation of microglia.

• Authors: Inge C M Hoogland, Jutka Yik, Dunja Westhoff, Joo-Yeon Engelen-Lee, Merche Valls Seron, Wing Kit Man, Judith H P M Houben-Weerts, Michael W T Tanck, David J van Westerloo, Tom van der Poll, Willem A van Gool, Diederik van de Beek
• Journal: Journal of neuroinflammation (J Neuroinflammation) Vol. 19 Issue 1 Pg. 94 (Apr 12 2022) ISSN: 1742-2094 [Electronic] England
• PMID: 35413868 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• Interleukin-6
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• alpha7 Nicotinic Acetylcholine Receptor

Topics

• Animals
• Escherichia coli (genetics)
• Escherichia coli Infections (metabolism)
• Inflammation (metabolism)
• Interleukin-6 (metabolism)
• Male
• Mice
• Microglia (metabolism)
• RNA, Messenger (metabolism)
• Sepsis
• Tumor Necrosis Factor-alpha (metabolism)
• alpha7 Nicotinic Acetylcholine Receptor (genetics, metabolism)