Fig. 6: Neuronal MCT2 in the dmPFC mediates the anti-depressive effects of L-lactate.

a Illustration of viral injections. Scale bars: left, 150 µm; right, 50 µm. b Reduced Mct2 mRNA level by shRNA against Mct2. n = 4 mice per group. Student’s t-test, t₍₆₎ = 7.928, p = 0.0002. c Compromised neuronal excitability of neurons in dmPFC of CaMKIIα-MCT2-KD mice. Left, representative firing traces. Scale bars: 0.2 s, 20 mV. Right, quantitative data. n = 15 and 14 neurons from 4 CaMKIIα-ctrl and 4 CaMKIIα-MCT2-KD mice. Two-way ANOVA, gene effect, F_(1,189) = 75.12, p = 0.0000. d, e Increased immobility duration (d) and decreased sucrose preference (e) of CaMKIIα-MCT2-KD mice. n = 12 mice per group. Student’s t-test, for FST, t₍₂₂₎ = 7.514, p = 0.0000; for SPT, t₍₂₂₎ = 3.417, p = 0.0025. f Experimental time scheme. g Diminished effect of L-lactate on neuronal excitability by MCT2 knockdown. Left, representative firing traces. Scale bars: 0.2 s, 20 mV. Right, quantitative data. n = 18, 22 and 19 neurons from 4 CaMKIIα-ctrl+vehicle, 4 CaMKIIα-MCT2-KD + vehicle mice and 4 CaMKIIα-MCT2-KD + L-lactate mice. Two-way ANOVA, for CaMKIIα-MCT2-KD + vehicle vs CaMKIIα-ctrl+vehicle, gene effect, F_(1,266) = 53.06, p = 0.0000; for CaMKIIα-MCT2-KD + L-lactate vs CaMKIIα-ctrl+vehicle, gene effect, F_(1,273) = 1.974, p = 0.1611. h, i Diminished effect of L-lactate on the immobility duration (h) and sucrose preference (i) by MCT2 knockdown. n = 8 mice per group. One-way ANOVA followed by Tukey’s post hoc test. For FST, F_(2,21) = 8.067, p = 0.0025. CaMKIIα-MCT2-KD + vehicle vs CaMKIIα-ctrl+vehicle, p = 0.0051; CaMKIIα-MCT2-KD + L-lactate vs CaMKIIα-ctrl+vehicle, p = 0.9853. For SPT, F_(2,21)= 5.041, p = 0.0163. CaMKIIα-MCT2-KD + vehicle vs CaMKIIα-ctrl+vehicle, p = 0.0142; CaMKIIα-MCT2-KD + L-lactate vs CaMKIIα-ctrl+vehicle, p = 0.5953. 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.