3-Hydroxybutyrate regulates energy metabolism and induces BDNF expression in cerebral cortical neurons.

ABSTRACT: During fasting and vigorous exercise, a shift of brain cell energy substrate utilization from glucose to the ketone 3-hydroxybutyrate (3OHB) occurs. Studies have shown that 3OHB can protect neurons against excitotoxicity and oxidative stress, but the underlying mechanisms remain unclear. Neurons maintained in the presence of 3OHB exhibited increased oxygen consumption and ATP production, and an elevated NAD⁺ /NADH ratio. We found that 3OHB metabolism increases mitochondrial respiration which drives changes in expression of brain-derived neurotrophic factor (BDNF) in cultured cerebral cortical neurons. The mechanism by which 3OHB induces Bdnf gene expression involves generation of reactive oxygen species, activation of the transcription factor NF-κB, and activity of the histone a

SUBMITTER: Marosi K 

PROVIDER: S-EPMC5123937 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature