Heptamethoxyflavone, a citrus flavonoid, enhances brain-derived neurotrophic factor production and neurogenesis in the hippocampus following cerebral global ischemia in mice

Neurosci Lett. 2012 Oct 24;528(2):190-5. doi: 10.1016/j.neulet.2012.08.079. Epub 2012 Sep 7.

Authors

Satoshi Okuyama¹, Naoko Shimada, Miki Kaji, Mayu Morita, Kazuhiro Miyoshi, Sona Minami, Yoshiaki Amakura, Morio Yoshimura, Takashi Yoshida, Sono Watanabe, Mitsunari Nakajima, Yoshiko Furukawa

Affiliation

¹ 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

PMID: 22985518
DOI: 10.1016/j.neulet.2012.08.079

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Astrocytes / metabolism
Astrocytes / pathology
Brain-Derived Neurotrophic Factor / biosynthesis*
Cyclic AMP Response Element-Binding Protein / metabolism
Doublecortin Domain Proteins
Flavonoids / pharmacology*
Glial Fibrillary Acidic Protein / metabolism
Hippocampus / drug effects*
Hippocampus / metabolism
Hippocampus / pathology
Ischemic Attack, Transient / metabolism*
Ischemic Attack, Transient / pathology
Male
Mice
Mice, Inbred C57BL
Microtubule-Associated Proteins / metabolism
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Neural Stem Cells / metabolism
Neural Stem Cells / pathology
Neurogenesis / drug effects
Neurons / metabolism
Neurons / pathology
Neuropeptides / metabolism
Phosphorylation

Substances

Brain-Derived Neurotrophic Factor
Creb1 protein, mouse
Cyclic AMP Response Element-Binding Protein
Doublecortin Domain Proteins
Flavonoids
Glial Fibrillary Acidic Protein
Microtubule-Associated Proteins
Neuropeptides
3,3',4',5,6,7,8-heptamethoxyflavone
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3