Expression of Fatty Acid-Binding Proteins in Adult Hippocampal Neurogenic Niche of Postischemic Monkeys

Expression of Fatty Acid-Binding Proteins in Adult Hippocampal Neurogenic Niche of Postischemic Monkeys
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DOI:
10.1002/hipo.20732
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发表时间:
2011-01-01
期刊:
影响因子:
3.5
通讯作者:
Yamashima, Tetsumori
Yamashima, Tetsumori
中科院分区:
医学3区
文献类型:
--
作者:
Boneva, Nadezhda B.;Kaplamadzhiev, Desislav B.;Yamashima, Tetsumori

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细胞内脂肪酸(FA)伴侣蛋白(称为FA结合蛋白(FABP))是一组已知参与细胞代谢过程如脂质储存、膜合成和β-氧化或协调转录程序的分子。然而,它们在成人神经发生中的作用仍然不清楚。在中枢神经系统(CNS)中表达的FABP是心脏型(FABP 3)、表皮型(FABP 5)和脑型(FABP 7)。这三种FABP对多不饱和脂肪酸(PUFA)具有不同的亲和力。最近,我们报道,GPR 40,游离脂肪酸,特别是多不饱和脂肪酸的受体,表达在成年猴的中枢神经系统和上调后,短暂的全脑缺血海马颗粒下区(SGZ),在成年期的神经原性龛。SGZ显示缺血后第2周祖细胞增殖高峰和GPR 40表达最高。由于FABP和GPR 40可能与成年神经发生密切相关,因此,我们研究了FABP 3、5和7在正常和缺血后成年猴SGZ中的表达。免疫印迹显示,FABP 5和FABP 7,但不是FABP 3,在缺血后第15天,与非缺血对照组相比,显着增加。免疫组化显示FABP 5在对照SGZ中几乎检测不到,但在缺血后15天大量表达。FABP 3、5和7在S-100 β阳性星形胶质细胞和巢蛋白阳性神经祖细胞中表达。然而,只有FABP 5和7被发现在溴脱氧尿苷(BrdU)阳性的新产生的细胞。FABPs最常与S-100 β阳性星形胶质细胞共表达,而β III-微管蛋白或多聚唾液酸化神经细胞粘附分子(PSA-NCAM)阳性的新生神经元在星形胶质细胞附近的表达没有三个FABPs。这些结果支持星形胶质细胞和/或神经祖细胞衍生的FABP作为调节成年灵长类动物脑中祖细胞生态位的分子机器的组成部分的作用。(C)2009威利-利斯公司
Intracellular fatty acid (FA) chaperones known as FA-binding proteins (FABPs) are a group of molecules known to participate in cellular metabolic processes such as lipid storage, membrane synthesis, and beta-oxidation or to coordinate transcriptional programs. However, their role in adult neurogenesis still remains obscure. The FABPs expressed in the central nervous system (CNS) are heart-type (FABP3), epidermal-type (FABP5), and brain-type (FABP7). These three FABPs possess a differential affinity for polyunsaturated fatty acids (PUFAs). Recently, we reported that GPR40, a receptor for free FAs and particularly for PUFAs, is expressed in the CNS of adult monkeys and upregulated after transient global brain ischemia in the hippocampal subgranular zone (SGZ), a neurogenic niche in adulthood. The SGZ showed a peak proliferation of progenitor cells and maximal expression of GPR40 during the second week after ischemia. As both FABPs and GPR40 might be closely related to the adult neurogenesis, here, we studied the expression of FABP 3, 5, and 7 in the SGZ, comparing normal and postischemic adult monkeys. Immunoblotting revealed that FABP5 and FABP7, but not FABP3, were significantly increased on day 15 after ischemia when compared with the nonischemic control. Immunohistochemistry showed that FABP5 was almost undetectable in the control SGZ but was abundant on day 15 after ischemia. FABP 3, 5, and 7 were expressed in S-100 beta-positive astrocytes and nestin-positive neural progenitors. However, only FABP 5 and 7 were found in bromodeoxyuridine (BrdU)-positive newly generated cells. FABPs were most frequently coexpressed with the S-100 beta-positive astrocytes, whereas beta III-tubulin-or polysialylated neural cell-adhesion molecule (PSA-NCAM)-positive newborn neurons in the vicinity of the astrocytes expressed none of the three FABPs. These results support a role of astrocyte- and/or neural progenitor-derived FABPs as components of the molecular machine regulating the progenitor cell niche in the adult primate brain. (C) 2009 Wiley-Liss, Inc.