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

Background: Development of neurodegeneration in older people has been associated with microglial cell activation triggered by systemic infection. We hypothesize that alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) plays an important role in regulation of this process. Methods: 8- to 10-week-old male wild-type (WT) and alpha 7nAChR knock-out (alpha 7nAChR(-/-)) 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 (lba-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 I ba-1 positive cell number or morphology and flow cytometry (CD11b, CD45 and CD14) of microglial cells between WT and alpha 7nAChR(-/-) mice after systemic infection. Infected alpha 7nAChR(-/-) mice showed significantly higher mRNA expression in brain for tumor necrosis factor alpha (TNF-alpha) 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 alpha 7nAChR during systemic infection led to an increased expression of INF-alpha 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.