Peripheral delivery of lactate induces hippocampal Bdnf expression and signaling. A, Intraperitoneal injections of lactate to reach equivalent levels to those reported in the blood after exercise lead to increases in hippocampal lactate. This increase is equivalent to the increase in hippocampal lactate observed after exercise. The number of hippocampi used for each group (control, lactate 117 mg/kg, or lactate 180 mg/kg) is 10, 9, and 7, respectively. **p < 0.01 (one-way ANOVA followed by the Dunnett's post-test; p = 0.003 for lactate 117 mg/kg vs control). B, Intraperitoneal injection of lactate (117 or 180 mg/kg) similar to levels reported during exercise significantly induces hippocampal Bdnf pI expression levels as measured by real-time RT-PCR. The expression was analyzed from the hippocampi of 5 control mice, 5 mice receiving 117 mg/kg lactate, and 5 mice receiving 180 mg/kg lactate. *p < 0.05 (one-way ANOVA followed by the Dunnett's multiple-comparison test; p = 0.0316 for lactate 117 mg/kg vs control and p = 0.0564 for lactate 180 mg/kg vs control). C, Intraperitoneal injection of lactate (117 mg/kg) does not induce hippocampal Bdnf pIV and coding expression levels as measured by real-time RT-PCR. The expression was analyzed from the hippocampi of 4 control mice and 4 mice receiving 117 mg/kg lactate. D, Representative Western blot image depicting the increase in BDNF protein levels and in phosphorylation in the BDNF receptor TRKBB (pTRKB) in the hippocampus of control animals compared with mice receiving 117 mg/kg of lactate. E, Quantification of the BDNF Western blot. *p < 0.05 (unpaired t test; p = 0.043 and df = 4). F, Quantification of the pTRKB Western blot. ****p < 0.0001 (unpaired t test; p = 0.000052 and df = 4). G, Representative Western blot image depicting the increase after 10 min in ZIF268 and ARC protein levels in the hippocampus of control animals compared with mice receiving 117 and 180 mg/kg of lactate. H, Quantification of the ZIF268 and ARC Western blots. *p < 0.05 (one-way ANOVA followed by the Dunnett's multiple-comparison test; ZIF268, p = 0.0196, df = 9 for lactate 180 mg/kg vs control; ARC, p = 0.0303, df = 7 for lactate 180 mg/kg vs control). I, Intraperitoneal injection of lactate (180 mg/kg) along with the lactate MCT transporters AR-C 155858 (50 nm/mouse) did not induce hippocampal Bdnf pI expression levels as measured by real-time RT-PCR. The expression was analyzed from the hippocampi of 5 control mice, 5 mice receiving 180 mg/kg lactate, and AR-C 155858 (50 nm/mouse). Significance was measured by unpaired t test (p = 0.9910 and df = 8).