Fig. 5: LDHA overexpression and L-lactate infusion alleviate depressive-like behaviors of CSDS-susceptible mice.

a Experimental time scheme. SIT social interaction test. b Illustration of viral injections. Solid arrows, GFP+ and S100β+; hollow arrows, GFP+ and NeuN+. Scale bars: 200 µm, 50 µm. c–e Representative Western blot images (c) and quantification (d, e). n = 4 mice per group. One-way ANOVA followed by Tukey’s post hoc test. for LDHA, F(2,9) = 8.304, p = 0.009. Sus+eGFP vs Res+eGFP, p = 0.009; Sus+LDHA-OE vs Sus+eGFP, p = 0.0392; Sus+LDHA-OE vs Res+eGFP, p = 0.6171. For LDHB, F(2,9) = 0.102, p = 0.9041. f Restored L-lactate levels. n = 6 mice per group. One-way ANOVA followed by Tukey’s post hoc test. F(2,15) = 6.191, p = 0.011. Sus+eGFP vs Res+eGFP, p = 0.0415; Sus+LDHA-OE vs Sus+eGFP, p = 0.0125. g Restored neuronal excitability. Left, representative firing traces. Scale bars: 0.2 s, 20 mV. Right, quantitative data. n = 15, 15, 16 neurons from 4 Res+eGFP, 4 Sus+eGFP, 4 Sus+LDHA-OE mice, respectively. Two-way ANOVA, for Sus+LDHA-OE vs Sus+eGFP, gene effect, F(1,203) = 26.68, p = 0.0000; for Sus+LDHA-OE vs Res+eGFP, gene effect, F(1,203) = 0.7911, p = 0.3748. h, i Reversed immobility duration (h) and sucrose preference (i). n = 11 mice per group. One-way ANOVA followed by Tukey’s post hoc test. For FST, F(2,30) = 7.3, p = 0.0026. Sus+eGFP vs Res+eGFP, p = 0.0033; Sus+LDHA-OE vs Sus+eGFP, p = 0.0166. For SPT, F(2,23) = 6.863, p = 0.0035. Sus+eGFP vs Res+eGFP, p = 0.0041; Sus+LDHA-OE vs Sus+eGFP, p = 0.0233. j Experimental time scheme. k, l Reversed immobility duration (k) and sucrose preference (l). n = 10 mice per group. One-way ANOVA followed by Tukey’s post hoc test. For FST, F(2,27) = 5.748, p = 0.0083. Sus+vehicle vs Res+vehicle, p = 0.0332; Sus+L-lactate vs Sus+vehicle, p = 0.0108. For SPT, F(2,27) = 7.805, p = 0.0021. Sus+vehicle vs Res+vehicle, p = 0.0049; Sus+L-lactate vs Sus+vehicle, p = 0.0062. Data were shown as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001; ns, no significant difference. Source data are provided as a Source Data file.