Fig. 6

Suppression of LTC4S-driven leukotriene C4 synthesis reverses radiation-induced anxiety and memory deficits. (A) Diagram of leukotriene synthesis pathway. (B) Upper panel: schematic of microglial repopulation and cranial irradiation procedures. Lower panel: heatmap of RNA-seq results showing the expression levels of genes related to leukotriene-C4 (LTC4) synthesis in the mPFC. (C) Quantification of LTC4 levels in the mPFC between groups. Data were presented as fold-change over Sham group (Sham: n = 11; R + CON: n = 13; R + PLX: n = 12; 1 outlier excluded from R + PLX group). (D) Schematic of the experimental designs. Following cranial irradiation, mice were administrated with TK05 (6 mg/kg, i.p.) for 1 week (R + TK05), followed by the behavioral tests conducted 2 weeks post irradiation. As a control, mice were administrated with saline for 1 week post irradiation (R + Veh). (E) Quantification of LTC4 levels in the mPFC between groups. Data were presented as fold-change over R + Veh group (R + Veh: n = 10; R + TK05: n = 8; 1 outlier excluded from R + TK05 group). (F) Quantification of the grooming duration in the splash test. (G) Quantification of time spent in the light box as a percentage of the total time in the D-L Box. (H) Quantification of the % Alteration in the Y maze test. (I) Quantification of the time spent in the center zone (as percentage of total time), the center distance travelled (as percentage of total distance travelled), and total distance travelled in the open field test. (F-I) R + Veh: n = 8; R + TK05: n = 9. Similar amount of male and female mice was used for each group and the results were combined for statistical analysis. Data are presented as mean ± s.e.m. and analyzed by one-way ANOVA with Tukey post hoc test (C), or Student’s t test (E-I)