鈥楶UFA-GPR40-CREB signaling鈥?hypothesis for the adult primate neurogenesis

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• 作者：Tetsumori Yamashima ; ^{yamashima215@gmail.com}
• 关键词：AC ; adenylyl cyclase ; AMPA ; 伪-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ; ARA ; arachidonic acid ; BDNF ; brain-derived neurotrophic factor ; BrdU ; bromodeoxyuridine ; [Ca2+]i ; intracellular Ca2+ concentration ; CaMK ; calmodulin-dependent kinase ; cAMP
• 刊名：Progress in Lipid Research
• 出版年：2012
• 期刊代码：132_01637827
• 类别：bio
• 出版时间：July, 2012
• 卷：51
• 期：3
• 页码：221-231
• 文件大小：1752 K

摘要

Despite the well-known effects of polyunsaturated fatty acids (PUFA) on synaptic plasticity, PUFA-modulated signaling mechanism is unknown especially in humans. In 2003, three groups reported that G protein-coupled receptor 40 (GPR40) induces Ca²⁺ mobilization in response to PUFA. Although GPR40 gene is abundantly expressed in the primate brain, it is negligible in the rodent brain. Diverse PUFA including docosahexaenoic acid (DHA) are in vitro ligands for GPR40, but nobody knows its downstream pathway. cAMP-response element binding protein (CREB) is a transcription factor transmitting extracellular signals to change gene expression. Although PUFA, transported by fatty acid binding proteins (FABP), directly phosphorylate CREB in rodents, hydrophobic PUFA cannot access to the nuclei in the primate neurons because of lack of a cargo protein. Ischemia-enhanced adult neurogenesis in monkeys showed concomitant upregulation of GPR40 and phosphorylated CREB, and localization of both in the neurogenic niche. Here, 鈥楶UFA-GPR40-CREB signaling鈥?hypothesis was highlighted as a regulator of adult neurogenesis specific for primates.