title: Sulforaphane epigenetically enhances neuronal BDNF expression and TrkB signaling pathways.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jisung
authors.initials: J
authors.lastname: Kim
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Siyoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Konkuk University, Seoul, Republic of Korea.
authors.forename: Bo-Ryoung
authors.initials: BR
authors.lastname: Choi
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hee
authors.initials: H
authors.lastname: Yang
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Youjin
authors.initials: Y
authors.lastname: Hwang
authors.affiliation: Department of Food Science, Nutrition, Hallym University, Chuncheon, South Korea.|Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Jung Han Yoon
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA.
authors.forename: Frank M
authors.initials: FM
authors.lastname: LaFerla
authors.affiliation: Department of Biological Sciences, Konkuk University, Seoul, Republic of Korea.
authors.forename: Jung-Soo
authors.initials: JS
authors.lastname: Han
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.|Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.|Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.|Research Institute of Bio Food Industry, Institute of Green Bio Science and Technology, Seoul National University, Pyeongchang, Republic of Korea.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.|Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D006657:Histones / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013454:Sulfoxides; D016708:Synaptophysin / Q000378:metabolism; D020813:Receptor, trkB
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000076122:Disks Large Homolog 4 Protein; D006657:Histones; D017879:Isothiocyanates; D008562:Membrane Glycoproteins; D008869:Microtubule-Associated Proteins; D011505:Protein-Tyrosine Kinases; D013454:Sulfoxides; D016708:Synaptophysin; C501447:Dlg4 protein, mouse; C079240:Mtap2 protein, mouse; C569015:Syp protein, mouse; C064371:Ntrk2 protein, mouse; D020813:Receptor, trkB; C016766:sulforaphane
keywords: Alzheimer's disease; Brain-derived neurotrophic factor; Histone deacetylase; Sulforaphane; Tyrosine kinase receptor B