Fig. 5: Vagal efferent pathway evokes hepatic LCN2 to induce anxiety disorders.
From: Stress increases hepatic release of lipocalin 2 which contributes to anxiety-like behavior in mice
a Theoretical model of pathways regulating liver LCN2 biosynthesis. b Relative concentrations of major serum inflammatory cytokines were unchanged between naïve and CRS mice. N = 6 mice in each group. c Undisturbed signaling pathway of IL-6 in hepatic tissues under CRS. N = 4 mice in each group. Stat1, signal transducer and activator of transcription 1; Il-6ra, interleukin-6 receptor alpha; Socs3, suppressor of cytokine signaling 3. Multiple t-test (in two-sided manner) was used for between-group comparison, with Holm–ŠÃdák method for correction. d Timeline for vagotomy assay. e The surgical site for subdiaphragmatic vagotomy, showing the separated and truncated vagal nerves before and at 21 days after dissection. f Immunofluorescent staining for liver LCN2 expression after vagotomy. Scale bar, 100 μm. g Liver Lcn2 gene transcript levels were suppressed by vagotomy under CRS but not in naïve condition. One-way ANOVA, F(3,16) = 400.4, P < 0.0001. h Vagotomy did not change basal level of LCN2 but helped to relive over-expression of LCN2 in serum under CRS. One-way ANOVA, F(3,16) = 73.68, P < 0.0001. i LCN2 levels in mPFC were also attenuated by vagotomy under CRS. One-way ANOVA, F(3,16) = 179.1, P < 0.0001. j Immunofluorescent staining for SLC22A17 and cFos in PrL after vagotomy and CRS. Scale bars, 500 μm on left image, and 100 μm in right panels. k Vagotomy abolished the elevated expression of Slc22a17 gene in CRS but not in naïve animals. One-way ANOVA, F(3,16) = 30.09, P < 0.0001. l CRS mice showed recovery of cortical neuron activity by vagotomy. One-way ANOVA, F(3,16) = 14.48, P < 0.0001. N = 5 mice in each group in (g–l). m Vagotomy did not affect baseline level of central zone duration, but antagonized anxiety-like behaviors in CRS animals. One-way ANOVA, F(3,24) = 12.21, P < 0.0001. n Avoidance toward the open arm in CRS group was attenuated by vagotomy. One-way ANOVA, F(3,24) = 13.92, P < 0.0001. o The duration in the light box of CRS mice was recovered after vagotomy. One-way ANOVA, F(3,24) = 24.18, P < 0.0001. N = 7 animals in each group in (m–o). Exact P-values were indicated using Tukey’s post-hoc comparison in (g–o). All data were presented as mean ± sem. Source data are provided as a Source Data file.
