Gastric vagal afferent signaling to the basolateral amygdala mediates anxiety-like behaviors in experimental colitis mice
Chin-Hao Chen, Tsung-Chih Tsai, Yi-Jen Wu, Kuei-Sen Hsu
Chin-Hao Chen, Tsung-Chih Tsai, Yi-Jen Wu, Kuei-Sen Hsu
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Research Article Neuroscience

Gastric vagal afferent signaling to the basolateral amygdala mediates anxiety-like behaviors in experimental colitis mice

Abstract

Inflammatory bowel disease (IBD) is a relapsing-remitting disorder characterized by chronic inflammation of the gastrointestinal (GI) tract. Anxiety symptoms are commonly observed in patients with IBD, but the mechanistic link between IBD and anxiety remains elusive. Here, we sought to characterize gut-to-brain signaling and brain circuitry responsible for the pathological expression of anxiety-like behaviors in male dextran sulfate sodium–induced (DSS-induced) experimental colitis mice. We found that DSS-treated mice displayed increased anxiety-like behaviors, which were prevented by bilateral GI vagal afferent ablation. The locus coeruleus (LC) is a relay center connecting the nucleus tractus solitarius to the basolateral amygdala (BLA) in controlling anxiety-like behaviors. Chemogenetic silencing of noradrenergic LC projections to the BLA reduced anxiety-like behaviors in DSS-treated mice. This work expands our understanding of the neural mechanisms by which IBD leads to comorbid anxiety and emphasizes a critical role of gastric vagal afferent signaling in gut-to-brain regulation of emotional states.

Authors

Chin-Hao Chen, Tsung-Chih Tsai, Yi-Jen Wu, Kuei-Sen Hsu

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Figure 1

DSS induces acute colitis in mice.

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DSS induces acute colitis in mice. (A) Schematic of the experimental tim...
(A) Schematic of the experimental timeline. Mice received 2% DSS in drinking water for 8 days, followed by a maintenance dose of 1% for 2 days. All groups were subjected to behavioral tests on day D8, D9 ,and D10 before sacrifice. (B) Body weights recorded during the experimental period (H2O: n = 10; DSS: n = 10). (C) Gross morphology image of H2O- or DSS-treated mice on D11 after administration. Arrows indicate: (arrow 1) shortened colon; (arrow 2) enlarged spleen; (arrow 3) shortened small intestine; (arrow 4) shrink cecum; and (arrow 5) stomach. (D–F) Quantification of colon length, small intestine length, and spleen weight on D11 in mice receiving H2O or DSS treatment (H2O: n = 10; DSS: n = 10). (G and H) H&E staining and histological score of colonic sections were assessed on D11 in mice receiving H2O or DSS treatment (H2O: n = 6; DSS: n = 6). M, mucosa layer; SM, submucosa layer; and ML, muscular layer. Scale bar: 200 μm. (I) Quantification of FITC-dextran permeability on D11 receiving H2O or DSS treatment (H2O: n = 10; DSS: n = 10). (J) DAI score was applied to evaluate the severity of DSS-induced colitis recorded from D1 to D10 (H2O: n = 10; DSS: n = 10). DAI score was calculated by total score (body weight + stool consistency + rectal bleeding). Data represent the mean ± SEM. **P < 0.01 and *** P < 0.001 by 2-way, repeated measures (RM) ANOVA (B and J), Mann-Whitney U test (D and H), and 2-tailed unpaired Student’s t test (E, F, and I).