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. 2019 Mar 27;39(13):2369–2382. doi: 10.1523/JNEUROSCI.1661-18.2019

Figure 5.

Figure 5.

Lactate induces Bdnf expression in an SIRT1-dependent manner. A, Voluntary exercise for 4 weeks significantly induced Sirt1 expression in the hippocampus as measured by real-time RT-PCR. The number of animals used for each group (control and exercise) is 3 and 5, respectively. *p < 0.05 (unpaired t test; p = 0.026 and df = 6). B, Representative Western blot image depicting the increase in SIRT1 protein levels in the hippocampus of control animals compared with exercising mice. C, Quantification of the SIRT1 Western blot. For control and exercise, n = 4. *p < 0.05 (unpaired t test; p = 0.0456 and df = 6). D, Representative Western blot image depicting the increase in SIRT1 protein levels in the hippocampus of mice receiving 117 mg/kg of lactate compared with mice receiving saline. E, Quantification of the SIRT1 Western blot. n = 5 saline injections; n = 6 lactate injections. **p < 0.005 (unpaired t test; p = 0.0077 and df = 9). F, Exercise and lactate (117 mg/kg) induce SIRT1 activity in hippocampal nuclear extracts. *p < 0.05 (unpaired t test; exercise, p = 0.05 and df = 3; lactate, p = 0.059 and df = 3). G, Three shRNA sequences significantly decrease Sirt1 mRNA expression as measured by real-time RT-PCR. *p < 0.05 (unpaired t test; seq 1, p = 0.0351 and df = 2; seq 4, p = 0.0045 and df = 2; seq 5, p = 0.05 and df = 2). H, SirtI knockdown abolishes the lactate-mediated increase in Bdnf pI expression. *p < 0.05 (unpaired t test; p = 0.0497 and df = 2 for Ctrl shRNA vs Ctrl shRNA + lactate 20 mm). I, Sirtinol, a SIRT1 inhibitor, reversed the lactate-mediated induction of Bdnf pI expression in primary neurons as measured by real-time RT-PCR. For controls, lactate (20 mm), sirtinol (50 μm), and lactate + sirtinol treatments, n = 6, n = 4, n = 6, and n = 6, respectively. Each replicate consisted of primary neurons obtained from different cultures and treated with fresh dilutions of the compounds for 4 h. One-way ANOVA followed by the Dunnett's post-test: *p < 0.05; **p < 0.01 (p = 0.0273 for control vs lactate, p = 0.0087 for sirtinol vs lactate, and p = 0.0130 for lactate + sirtinol vs lactate).