Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan.
Neurosci Lett. 2012 Oct 24;528(2):190-5. doi: 10.1016/j.neulet.2012.08.079. Epub 2012 Sep 7.
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.
在本研究中，我们使用短暂性全脑缺血小鼠模型，表明：（1）柑橘类黄酮 3,5,6,7,8,3',4'-七甲氧基黄酮（HMF）可在缺血后诱导海马中细胞外信号调节激酶 1/2（ERK1/2）和 cAMP 反应元件结合蛋白（CREB）的磷酸化；（2）HMF 可增加海马齿状回中脑源性神经营养因子（BDNF）的表达，BDNF 是中枢神经系统中代表性的神经营养因子，大多数 BDNF 阳性细胞也与抗胶质纤维酸性蛋白（成熟星形胶质细胞的主要中间丝蛋白之一）染色；（3）HMF 可增加齿状回下脑室区或下颗粒层中的双皮质素阳性神经前体细胞。这些结果表明，HMF 具有诱导星形胶质细胞中 BDNF 产生和增强脑缺血后神经发生的能力，这可能是通过激活 ERK1/2 和 CREB 介导的。
