Beta-Hydroxybutyrate Enhances BDNF Expression by Increasing H3K4me3 and Decreasing H2AK119ub in Hippocampal Neurons

Frontiers in Neuroscience
Erling HuXiaoyun Lu

Abstract

Neurological evidence suggests that beta-hydroxybutyrate (BHBA) has positive effects on the central nervous system. Previous studies have explored the molecular mechanisms by which BHBA affects different brain functions, but the effects of BHBA on epigenetic modifications remain elusive. Here, we showed that BHBA enhanced brain-derived neurotrophic factor (BDNF) expression by increasing H3K4me3 and decreasing H2AK119ub occupancy at the Bdnf promoters I, II, IV, and VI in hippocampal neurons. Moreover, BHBA treatment induced the upregulation of H3K4me3 and downregulation of H2AK119ub on the global level, both of which were dependent on the L-type calcium channel. Additionally, the BHBA-activated L-type calcium channel subsequently triggered the activation of Ca2+/CaMKII/CREB signaling, and promoted the binding of p-CREB and CBP to Bdnf promoters. These results indicate that BHBA regulates cellular signaling and multiple histone modifications to cooperatively modulate BDNF, suggesting a wide range of regulatory effects of BHBA in the central nervous system.

References

Sep 17, 2003·The Journal of Clinical Investigation·Kim TieuSerge Przedborski
May 5, 2004·Neurobiology of Aging·Mark A RegerSuzanne Craft
Sep 24, 2004·Nature·Hengbin WangYi Zhang
Mar 15, 2005·Biomacromolecules·Shan ChengGuo-Qiang Chen
Dec 7, 2006·Journal of Neuroscience Research·Tamara AidTõnis Timmusk
Dec 30, 2008·Biomaterials·Xiang-Hui ZouGuo-Qiang Chen
Apr 7, 2009·Current Opinion in Genetics & Development·Jürg Müller, Peter Verrijzer
Oct 6, 2010·Neuron·Narinobu JugeYoshinori Moriyama
Dec 12, 2012·Trends in Neurosciences·Andrew Lutas, Gary Yellen
May 20, 2014·Nature Structural & Molecular Biology·Reinhard KalbJürg Müller
Mar 15, 2015·Trends in Molecular Medicine·Stefan Offermanns, Markus Schwaninger
Apr 4, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mira JakovcevskiSchahram Akbarian
Oct 1, 2015·Nature Reviews. Molecular Cell Biology·Neil P BlackledgeRobert J Klose
Mar 1, 2016·Neurobiology of Aging·Jun Xiang YinJiong Shi
Apr 23, 2016·Molecular Cell·Zhongyu XieYingming Zhao
Jun 13, 2017·The Journal of Clinical Investigation·Qing LiXiao Yu
Aug 23, 2017·Annual Review of Nutrition·John C Newman, Eric Verdin

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Methods Mentioned

BETA
acetylation
Immunoprecipitation
ChIP
PCR
RNA-seq
ChIP-seq
ubiquitination

Software Mentioned

GraphPad Prism
GraphPad
ImageJ

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