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Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate

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 expr...

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Autores principales: Sleiman, Sama F, Henry, Jeffrey, Al-Haddad, Rami, El Hayek, Lauretta, Abou Haidar, Edwina, Stringer, Thomas, Ulja, Devyani, Karuppagounder, Saravanan S, Holson, Edward B, Ratan, Rajiv R, Ninan, Ipe, Chao, Moses V
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915811/
https://www.ncbi.nlm.nih.gov/pubmed/27253067
http://dx.doi.org/10.7554/eLife.15092
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author Sleiman, Sama F
Henry, Jeffrey
Al-Haddad, Rami
El Hayek, Lauretta
Abou Haidar, Edwina
Stringer, Thomas
Ulja, Devyani
Karuppagounder, Saravanan S
Holson, Edward B
Ratan, Rajiv R
Ninan, Ipe
Chao, Moses V
author_facet Sleiman, Sama F
Henry, Jeffrey
Al-Haddad, Rami
El Hayek, Lauretta
Abou Haidar, Edwina
Stringer, Thomas
Ulja, Devyani
Karuppagounder, Saravanan S
Holson, Edward B
Ratan, Rajiv R
Ninan, Ipe
Chao, Moses V
author_sort Sleiman, Sama F
collection PubMed
description 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
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spelling pubmed-49158112016-06-23 Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate Sleiman, Sama F Henry, Jeffrey Al-Haddad, Rami El Hayek, Lauretta Abou Haidar, Edwina Stringer, Thomas Ulja, Devyani Karuppagounder, Saravanan S Holson, Edward B Ratan, Rajiv R Ninan, Ipe Chao, Moses V eLife Cell Biology 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 eLife Sciences Publications, Ltd 2016-06-02 /pmc/articles/PMC4915811/ /pubmed/27253067 http://dx.doi.org/10.7554/eLife.15092 Text en © 2016, Sleiman et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Sleiman, Sama F
Henry, Jeffrey
Al-Haddad, Rami
El Hayek, Lauretta
Abou Haidar, Edwina
Stringer, Thomas
Ulja, Devyani
Karuppagounder, Saravanan S
Holson, Edward B
Ratan, Rajiv R
Ninan, Ipe
Chao, Moses V
Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate
title Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate
title_full Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate
title_fullStr Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate
title_full_unstemmed Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate
title_short Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate
title_sort exercise promotes the expression of brain derived neurotrophic factor (bdnf) through the action of the ketone body β-hydroxybutyrate
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915811/
https://www.ncbi.nlm.nih.gov/pubmed/27253067
http://dx.doi.org/10.7554/eLife.15092
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