Fig. 4.

LDN/OSU-215111 normalizes mood impairments after symptom onset. (A) Experimental procedure. Littermate-matched mice were randomly divided into two groups: control and GWI. GWI mice were exposed to GW agents and stress for six weeks. At five-months post-exposure, all mice were assessed for anxiety and depression (“before”). After the behavioral tests, GWI mice received LDN/OSU-215111, and control mice received vehicle. After one-month of treatment, behavioral tests were repeated (“after”). Following treatment cessation, behavioral tests were conducted again one-month later (“stop”). (B–F) Assessment of anxiety and depression. Overall, GWI mice exhibited anxiety- and depression-like behaviors before LDN/OSU-215111 treatment (“before”), and these behaviors significantly improved after the treatment (“after”). The effects of LDN/OSU-215111 lasted one month after treatment cessation (“stop”). The asterisk (*) indicates the difference between control and GWI mice, and the number sign (#) indicates the difference between “before” and “after”, or “before” and “stop” in GWI mice. n = 17–21 males and n = 14–15 females each group. Data are presented as mean ± SD. Statistics are based on a two-way ANOVA comparison followed by uncorrected Fisher's LSD method for pairwise comparisons. A repeated measures ANOVA was used to compare “before” with “after”, or “before” with “stop” within GWI group. F and P values for repeated measures ANOVA are shown. F_treatment indicates the F value among “before, after and stop” within the GWI group. *P < 0.05; **P < 0.01. ^#P < 0.05; ^##P < 0.01; ^###P < 0.001.