| First Author | Hoogland ICM | Year | 2022 |
| Journal | J Neuroinflammation | Volume | 19 |
| Issue | 1 | Pages | 94 |
| PubMed ID | 35413868 | Mgi Jnum | J:324016 |
| Mgi Id | MGI:7262329 | Doi | 10.1186/s12974-022-02452-8 |
| Citation | Hoogland ICM, et al. (2022) Microglial cell response in alpha7 nicotinic acetylcholine receptor-deficient mice after systemic infection with Escherichia coli. J Neuroinflammation 19(1):94 |
| abstractText | BACKGROUND: Development of neurodegeneration in older people has been associated with microglial cell activation triggered by systemic infection. We hypothesize that alpha7 nicotinic acetylcholine receptor (alpha7nAChR) plays an important role in regulation of this process. METHODS: 8- to 10-week-old male wild-type (WT) and alpha7nAChR knock-out (alpha7nAChR(-/-)) 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 alpha7nAChR(-/-) mice after systemic infection. Infected alpha7nAChR(-/-) 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 alpha7nAChR during systemic infection led to an increased expression of TNF-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. |
