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

Sulforaphane epigenetically enhances neuronal BDNF expression and TrkB signaling pathways.

Author information

1
WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
2
Department of Biological Sciences, Konkuk University, Seoul, Republic of Korea.
3
Department of Food Science, Nutrition, Hallym University, Chuncheon, South Korea.
4
Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
5
Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA.
6
Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
7
Research Institute of Bio Food Industry, Institute of Green Bio Science and Technology, Seoul National University, Pyeongchang, Republic of Korea.
8
Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.

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

PMID:
27735126
DOI:
10.1002/mnfr.201600194
[Indexed for MEDLINE]

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