Beta-hydroxybutyrate Promotes the Expression of BDNF in Hippocampal Neurons under Adequate Glucose Supply.
Level 5 - mechanism / opinion, no new human data
Bench and animal research (in vivo mouse model and in vitro cell culture).
PubMed 29966721 · doi:10.1016/j.neuroscience.2018.06.036
What was done
Researchers investigated whether beta-hydroxybutyrate (BHBA) induces brain-derived neurotrophic factor (BDNF) expression in the presence of adequate glucose. They administered BHBA to mice fed a normal diet and exposed primary mouse hippocampal neurons and the HT22 hippocampal cell line in vitro to physiological concentrations of BHBA (0.02 to 2 mM). Epigenetic and signaling mechanisms involving cAMP/PKA, CREB phosphorylation, and histone H3 Lysine 27 (H3K27) acetylation and demethylation at Bdnf promoters were analyzed.
What was found
BHBA administration induced BDNF expression in the hippocampus of mice on a normal diet. In vitro, BHBA at 0.02–2 mM significantly increased BDNF expression in primary hippocampal neurons and HT22 cells under normal glucose conditions. The abstract reports no exact numerical effect sizes, fold-changes, or p-values. Mechanistically, BDNF transcription was linked to cAMP/PKA-mediated phosphorylation of CREB (S133), increased H3K27ac binding at Bdnf promoters I, II, IV, and VI, decreased H3K27me3 binding at promoters II and VI, and increased levels of the demethylase JMJD3.
Why it matters
This study suggests that beta-hydroxybutyrate can stimulate neurotrophic factor production and epigenetic changes independently of caloric or carbohydrate restriction.
Limits
The abstract lacks sample sizes, specific dosage regimens for the in vivo mouse arm, and exact quantitative effect sizes. Findings are limited to rodent cells and mouse models, precluding direct extrapolation to human brain physiology or clinical outcomes.
Cited by
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