Sulforaphane epigenetically enhances neuronal BDNF expression and TrkB signaling pathways

Mol Nutr Food Res. 2017 Feb;61(2). doi: 10.1002/mnfr.201600194. Epub 2016 Nov 30.

Abstract

Scope: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. We investigated the effect of sulforaphane, a hydrolysis product of glucoraphanin present in Brassica vegetables, on neuronal BDNF expression and its synaptic signaling pathways.

Methods and results: Mouse primary cortical neurons and a triple-transgenic mouse model of Alzheimer's disease (3 × Tg-AD) were used to study the effect of sulforaphane. Sulforaphane enhanced neuronal BDNF expression and increased levels of neuronal and synaptic molecules such as MAP2, synaptophysin, and PSD-95 in primary cortical neurons and 3 × Tg-AD mice. Sulforaphane elevated levels of synaptic TrkB signaling pathway components, including CREB, CaMKII, ERK, and Akt in both primary cortical neurons and 3 × Tg-AD mice. Sulforaphane increased global acetylation of histone 3 (H3) and H4, inhibited HDAC activity, and decreased the level of HDAC2 in primary cortical neurons. Chromatin immunoprecipitation analysis revealed that sulforaphane increased acetylated H3 and H4 at BDNF promoters, suggesting that sulforaphane regulates BDNF expression via HDAC inhibition.

Conclusion: These findings suggest that sulforaphane has the potential to prevent neuronal disorders such as Alzheimer's disease by epigenetically enhancing neuronal BDNF expression and its TrkB signaling pathways.

Keywords: Alzheimer's disease; Brain-derived neurotrophic factor; Histone deacetylase; Sulforaphane; Tyrosine kinase receptor B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Disease Models, Animal
  • Disks Large Homolog 4 Protein / metabolism
  • Epigenesis, Genetic / drug effects*
  • Female
  • Histones / metabolism
  • Isothiocyanates / pharmacology*
  • Membrane Glycoproteins / metabolism*
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Microtubule-Associated Proteins / metabolism
  • Neurons / drug effects*
  • Neurons / metabolism
  • Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction / drug effects
  • Synaptophysin / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Histones
  • Isothiocyanates
  • Membrane Glycoproteins
  • Microtubule-Associated Proteins
  • Mtap2 protein, mouse
  • Synaptophysin
  • Syp protein, mouse
  • Ntrk2 protein, mouse
  • Protein-Tyrosine Kinases
  • sulforafan