Sleiman · eLife 2016 · Preclinical animal and mechanistic laboratory study · n=?

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

Cited 793 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Preclinical animal and bench research

PubMed 27253067 · doi:10.7554/eLife.15092 · record verified 2026-08-26

What was done

Investigated the molecular pathway linking exercise to brain-derived neurotrophic factor (Bdnf) induction in mice (Mus musculus). The authors assessed the effect of the exercise metabolite beta-hydroxybutyrate on Bdnf promoters (focusing on promoter I) and histone deacetylases HDAC2 and HDAC3, evaluated hippocampal Bdnf expression following direct intraventricular administration of beta-hydroxybutyrate, and measured synaptic neurotransmitter release via electrophysiology with TrkB receptor dependency testing.

What was found

The abstract provides no exact numerical data or effect sizes. Qualitatively, beta-hydroxybutyrate selectively inhibited HDAC2 and HDAC3 to activate Bdnf promoters (particularly promoter I), direct ventricular delivery increased hippocampal Bdnf expression, and electrophysiological testing showed an increase in neurotransmitter release that was dependent on the TrkB receptor.

Why it matters

The study identifies an endogenous biochemical link between peripheral exercise metabolism and central neuroplasticity, demonstrating that exercise-induced ketone bodies can directly trigger hippocampal BDNF expression via HDAC inhibition.

Limits

All findings are from rodent and in vitro models, limiting direct translation to humans. The abstract does not report sample sizes, concentrations tested, statistical comparisons, or numerical outcomes.

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