Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate
By Sama F. Sleiman, J. Henry, Rami Al-Haddad, Lauretta El Hayek, Edwina Abou Haidar, Thomas Stringer, Devyani Ulja, S. Karuppagounder, E. Holson, R. Ratan and 2 more. eLife, 2016
728 citations recorded by the source corpus.
Exercise induces beneficial responses in the brain, which is accompanied by an increase in BDNF, a trophic factor associated with cognitive improvement and the alleviation of depression and anxiety. However, the exact mechanisms whereby physical exercise produces an induction in brain Bdnf gene expression are not well understood. While pharmacological doses of HDAC inhibitors exert positive effects on Bdnf gene transcription, the inhibitors represent small molecules that do not occur in vivo. Here, we report that an endogenous molecule released after exercise is capable of inducing key promoters of the Mus musculus Bdnf gene. The metabolite β-hydroxybutyrate, which increases after prolonged exercise, induces the activities of Bdnf promoters, particularly promoter I, which is activity-dependent. We have discovered that the action of β-hydroxybutyrate is specifically upon HDAC2 and HDAC3, which act upon selective Bdnf promoters. Moreover, the effects upon hippocampal Bdnf expression were observed after direct ventricular application of β-hydroxybutyrate. Electrophysiological measurements indicate that β-hydroxybutyrate causes an increase in neurotransmitter release, which is dependent upon the TrkB receptor. These results reveal an endogenous mechanism to explain how physical exercise leads to the induction of BDNF. DOI: http://dx.doi.org/10.7554/eLife.15092.001
Subfields: Geriatrics and Gerontology, Physiology
View Paper: https://www.semanticscholar.org/paper/34ed9493a66db95e407612ab8e7a019d510b41cd
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In Physiology
Citations in the corpus
- The Effects of Acute Exercise on Mood, Cognition, Neurophysiology, and Neurochemical Pathways: A Review (2016, background): “New findings are emerging that the wellstudied ketone body, -hydroxybutyrate, secreted by the liver after exercise [167] and known to pass the blood brain barrier, activates central BDNF promoters and increases BDNF gene transcription in the hippocampus by inhibiting the histone deacetylases (HDAC),”
- Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States (2018, background): “CREB, NF-kB, and NRF2 induce the expression of genes encoding proteins that mitigate cellular stress and eliminate or repair damaged molecules.”
- Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics (2017, background): “268 Cell Metabolism 25, February 7, 2017 sive to brain derived neutrophic factor (BDNF) (Marosi et al., 2016; Sleiman et al., 2016) or to oxidative stress (Shimazu et al.”