title: Heptamethoxyflavone, a citrus flavonoid, enhances brain-derived neurotrophic factor production and neurogenesis in the hippocampus following cerebral global ischemia in mice.
abstract: In the present study using a transient global ischemia mouse model, we showed that (1) a citrus flavonoid 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) induced the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and cAMP response element-binding protein (CREB) in the hippocampus after ischemia; (2) HMF increased the expression of brain-derived neurotrophic factor (BDNF), a representative neurotrophic factor in the central nervous system, in the hippocampal dentate gyrus, and most BDNF-positive cells were also stained with anti-glial fibrillary acidic protein (one of the major intermediate filament proteins of mature astrocytes) and (3) HMF increased doublecortin positive neuronal precursor cells in the dentate gyrus subventricular zone or subgranular zone. These results suggest that HMF has the ability to induce BDNF production in astrocytes and enhance neurogenesis after brain ischemia, which may be mediated by activation of ERK1/2 and CREB.
authors.affiliation: Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. sokuyama@cc.matsuyama-u.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okuyama
authors.forename: Naoko
authors.initials: N
authors.lastname: Shimada
authors.forename: Miki
authors.initials: M
authors.lastname: Kaji
authors.forename: Mayu
authors.initials: M
authors.lastname: Morita
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Miyoshi
authors.forename: Sona
authors.initials: S
authors.lastname: Minami
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Amakura
authors.forename: Morio
authors.initials: M
authors.lastname: Yoshimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Sono
authors.initials: S
authors.lastname: Watanabe
authors.forename: Mitsunari
authors.initials: M
authors.lastname: Nakajima
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D005419:Flavonoids / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism; D010766:Phosphorylation
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D000089622:Doublecortin Domain Proteins; D005419:Flavonoids; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; C059294:3,3',4',5,6,7,8-heptamethoxyflavone; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3