Evidence map›Paper›PMID 27253067›Full record

ArticleeLife2016

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

Sama F Sleiman, Jeffrey Henry, Rami Al-Haddad, Lauretta El Hayek, Edwina Abou Haidar, Thomas Stringer, Devyani Ulja, Saravanan S Karuppagounder, Edward B Holson, Rajiv R Ratan and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 479 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
479citing papers in PubMed, 9 pooled it
31.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

479 citing papers in PubMed, 9 syntheses or guidelines pooled it, 741 citations in OpenAlex.

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  13. Exercise in Pregnancy and Risk of Postpartum Depression: A Randomised Controlled Trial.BJOG : an international journal of obstetrics and gynaecology · 2026
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419 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Sama F SleimanDepartment of Natural Sciences, Lebanese American University, Byblos, Lebanon.
Jeffrey HenrySkirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, United States.
Rami Al-HaddadDepartment of Natural Sciences, Lebanese American University, Byblos, Lebanon.
Lauretta El HayekDepartment of Natural Sciences, Lebanese American University, Byblos, Lebanon.
Edwina Abou HaidarDepartment of Natural Sciences, Lebanese American University, Byblos, Lebanon.
Thomas StringerSkirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, United States.
Devyani UljaSkirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, United States.
Saravanan S KaruppagounderBurke Medical Research Institute, White Plains, United States.
Edward B HolsonStanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, United States.
Rajiv R RatanBurke Medical Research Institute, White Plains, United States.
Ipe NinanSkirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, United States.
Moses V ChaoSkirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, United States.ORCID 0000-0002-6969-3744
NYU Langone Health · USLebanese American University · LBCornell University · USBroad Institute · US

Funding

MOLECULAR BIOLOGY OF THE NERVE GROWTH FACTOR RECEPTORR01NS021072 · NINDS · WEILL MEDICAL COLLEGE OF CORNELL UNIV · PI CHAO, MOSES VICTOR · 1985 to 2015
$5.8M
Gamma-Secretase cleavage of the p75 receptorR01AG025970 · NIA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CHAO, MOSES VICTOR · 2006 to 2016
$3.3M
Mechanisms of developmental regulation of affective behaviorsR01HD076914 · NICHD · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI NINAN, IPE · 2014 to 2019
$1.8M
Molecular Analysis of Neurotrophin ActionR56NS021072 · NINDS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CHAO, MOSES VICTOR · 2011 to 2017
$882k
Regulation of BACE1 by trophic factor signalingR56AG025970 · NIA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CHAO, MOSES VICTOR · 2018 to 2018
$494k
NIA NIH HHS R01 AG025970NIA NIH HHS R56 AG025970NICHD NIH HHS R01 HD076914NINDS NIH HHS R01 NS021072NINDS NIH HHS R56 NS021072
6 · The paper itself

Abstract

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.

Indexed as

3-Hydroxybutyric AcidAcetylationAnimalsBrain-Derived Neurotrophic FactorCells, CulturedGene Expression RegulationHippocampusHistone Deacetylase 2Histone Deacetylase 3Histone DeacetylasesHistonesMaleMiceMice, Inbred C57BLNeuronsNeurotransmitter Agents3-Hydroxybutyric AcidBrain-Derived Neurotrophic FactorHdac2 protein, mouseHistone Deacetylase 2Histone Deacetylase 3Histone DeacetylasesHistonesNeurotransmitter AgentsReceptor, trkBbdnfbeta hydroxybutyratecell biologyepigeneticsHDAC inhibitorsmousephysical exercise

Identifiers

PMID27253067
PMCPMC4915811
OpenAlexW2411915694

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.