Expression of free fatty acid receptor GPR40 in the neurogenic niche of adult monkey hippocampus

Expression of free fatty acid receptor GPR40 in the neurogenic niche of adult monkey hippocampus
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DOI:
10.1002/hipo.20393
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发表时间:
2008-01-01
期刊:
影响因子:
3.5
通讯作者:
Yamashima, Tetsurnori
Yamashima, Tetsurnori
中科院分区:
医学3区
文献类型:
--
作者:
Ma, Dexuan;Lu, Li;Yamashima, Tetsurnori

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多不饱和游离脂肪酸(PUFAs)已知对大脑的发育、维持和功能起着关键作用。最近,我们报道了G蛋白偶联受体40(GPR40),一种PUFA受体,在成年灵长类动物的中枢神经系统包括海马体中都有表达。这就开启了一种可能性,即PUFA可能作为细胞外信号分子作用于GPR40受体来调节神经元功能。在此我们研究了正常和缺血后条件下成年猴海马体神经发生微环境中GPR40的蛋白表达。对免疫染色切片进行共聚焦激光显微镜分析显示,在齿状回(DG)的颗粒下区(SGZ)的神经祖细胞、未成熟神经元、星形胶质细胞和内皮细胞中存在GPR40免疫反应性;齿状回的颗粒下区是成年大脑中一个众所周知的神经发生微环境。免疫印迹分析表明,与对照组相比,全脑缺血后第二周GPR40蛋白显著增加。这与通过免疫荧光成像检测到的颗粒下区GPR40阳性细胞在缺血后的增加是相符的。结合我们之前关于缺血后颗粒下区祖细胞上调的发现,目前的数据表明,像二十二碳六烯酸这样的PUFA可能通过GPR40来调节灵长类动物成年海马体的神经发生。(C)2007威利 - 利斯公司
Polyunsaturated free fatty acids (PUFAs) are known to play critical roles for the development, maintenance, and function of the brain. Recently, we reported that G-protein coupled receptor 40 (GPR40), one type of PUFA receptors, is expressed throughout the adult primate central nervous system including the hippocampus. This opens a possibility that PUFA might act as extracellular signaling molecules at the GPR40 receptor to regulate neuronal function. Here we studied protein expression of GPR40 in the neurogenic niche of the adult monkey hippocampus under normal and postischemic conditions. Confocal laser microscope analysis of immunostained sections revealed GPR40 immunoreactivity in neural progenitors, immature neurons, astrocytes and endothelial cells of the subgranular zone (SGZ) of the dentate gyrus (DG); a well-known neurogenic niche within the adult brain. Immunoblotting analysis showed that the GPR40 protein increased significantly in the second week after global cerebral ischemia as compared with the control. This was compatible with the postischemic increment of GPR40-positive cells in the SGZ as detected by immunofluorescence imaging. Taken together with our previous findings of the SGZ progenitor cell upregulation after ischemia, the present data suggest that PUFA such as docosahexaenoic acid may act via GPR40 to regulate adult hippocampal neurogenesis in primates. (C) 2007 Wiley-Liss, Inc.