Lactate mediates the effects of exercise on learning and memory through SIRT1-dependent activation of hippocampal brain-derived neurotrophic factor (BDNF)

• DOI: 10.1523/jneurosci.1661-18.2019
• Publication Date: 2019-01-29T00:48:50Z
• Authors: Lauretta El Hayek; Mohamad Khalifeh; Victor Zibara; Rawad Abi Assaad; Nancy Emmanuel; Nabil Karnib; Rim El-Ghandour; Patrick Nasrallah; Maria Bilen; Pascale Ibrahim; Joe Younes; Edwina Abou Haidar; Nour Barmo; Vanessa Jabre; Joseph S. Stephan; Sama F. Sleiman
• Keywords: Physical exercise

Exercise promotes learning and memory formation. These effects depend on increases in hippocampal BDNF, a growth factor associated with cognitive improvement the alleviation of depression symptoms. Identifying molecules that are produced during exercise mediate <i>Bdnf</i> expression will allow us to harness therapeutic potential exercise. Here, we report an endogenous molecule male mice induces <i>Mus musculus Bdnf</i> gene The metabolite lactate, which is released by muscles, crosses blood–brain barrier TRKB signaling hippocampus. Indeed, find lactate-dependent BDNF improved spatial retention. action lactate dependent activation Sirtuin1 deacetylase. SIRT1 levels transcriptional coactivator PGC1a secreted FNDC5, known expression. results reveal mechanism explain how physical leads induction identify as may have value for CNS diseases disrupted. <b>SIGNIFICANCE STATEMENT</b> It established formation alleviates symptoms depression. mediated through inducing Understanding identifying this design strategies can mimic brain, especially patients disorders characterized decrease who cannot because their conditions. We exercise, BDNF-dependent manner. Our work identifies component “exercise pill.”