Fig. 1

Prior exposure to DSS-induced colitis led to neuroinflammation. a Schematic diagram of experimental design. Mice were given normal (control) or 2% DSS in drinking water for 6 days (Day 0–6), then switched to normal drinking water and allowed to recover, mimicking clinical remission. Mice were then subjected to conditioned fear (CF) tests on days 15–16. For in vivo study, n = 10, 12, 9, and 8 for male-control, male-DSS, female-control, and female-DSS groups, respectively. b Disease activities including fecal consistency and rectal pathologies were monitored. Data were analyzed with two-way ANOVA (treatment × repeated measures) followed by Tukey’s multiple comparisons test. ^#p < 0.05 male-DSS vs. female-DSS. c, d DSS-exposed mice showed significantly impaired contextual fear memory in both male and female mice (c), but comparable auditory fear memory (d). Two-way ANOVA (treatment and gender as independent factors) followed by Tukey’s multiple comparisons test. e Representative images of the hippocampal regions of mice on Day 17. DSS-exposed mice showed increased astrogliosis (increase in abundance and cell size of GFAP-labeled astrocytes (green). Sections were counterstained with DAPI (blue). Scale bar 50 μm. Images were taken from 3 stained sections per brain, 3 brains per group. Images were processed and the areas of GFAP-labeled cells were quantified with ImageJ. Quantitative PCR analyses of expression of Nfkb, Trem-2, Gfap, IL-1b, S100a8, and Bdnf in the hippocampus collected from control and DSS-treated mice on Day 10, 17, and 42 (f–k respectively; n = 4 per group). One-way ANOVA followed by Tukey’s multiple comparisons test, *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001. All data were presented as mean ± SD, except for 1b where disease scores were presented as mean ± SEM, for clarity