Fig. 7: Signaling pathways that are influenced by Muscimol.
To investigate which signaling pathways are affected by modulation of the GABAA-receptor, 44 signaling proteins were tested using DigiWest. A Overview of the expression of all signaling molecules investigated. Each row represents a sample of wild type animals four hours after LPS inhalation, and each column represents the normalized expression of a signaling protein. The expression level is color-coded from red (upregulated) to black, to green (downregulated). Samples from each of four animals in the control group without LPS, four hours after LPS, and in the treatment group with Muscimol were tested. B Schematic representation of Muscimol (illustrated as M) inhibiting the Interleukin-6 (IL-6) signaling pathway. Muscimol blocks the phosphorylation of Extracellular-signal Regulated Kinase 1/2 (ERK1/2), but not phosphorylation of signal transducer and activator of transcription 3 (STAT3). Created with biorender.com. C Schematic representation of Muscimol (M) inhibiting the Phosphoinositide 3-kinase (PI3K) signaling pathway. Muscimol activates Phosphatase and tensin homolog (PTEN), which leads to less AKT and more activated Glycogen synthase kinase 3 (GSK3). GSK3 inhibits β-catenin and therefore transcription. Created with biorender.com. D Shown are the signaling proteins with significant results of statistical analysis between the control groups without and with LPS. E Statistical analyses were performed by unpaired t-tests. Signaling proteins with statistically significant effect when comparing mice four hours after LPS with the treatment group receiving Muscimol. F String analysis was performed to determine the relationship between selectins, integrins, the proinflammatory cytokine IL-6 and the signaling proteins whose expression was significantly altered by Muscimol treatment.
