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Sulforaphane epigenetically enhances neuronal BDNF expression and TrkB signaling pathways
Author(s) -
Kim Jisung,
Lee Siyoung,
Choi BoRyoung,
Yang Hee,
Hwang Youjin,
Park Jung Han Yoon,
LaFerla Frank M.,
Han JungSoo,
Lee Ki Won,
Kim Jiyoung
Publication year - 2017
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201600194
Subject(s) - sulforaphane , tropomyosin receptor kinase b , brain derived neurotrophic factor , chromatin immunoprecipitation , neurotrophic factors , chemistry , microbiology and biotechnology , neuroscience , neurotrophin , biology , gene expression , biochemistry , receptor , promoter , gene
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.