A putative link of PUFA, GPR40 and adult-born hippocampal neurons for memory
A putative link of PUFA, GPR40 and adult-born hippocampal neurons for memory
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DOI：
10.1016/j.pneurobio.2007.11.002
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发表时间：
2008-02
影响因子：
6.7
通讯作者：
T. Yamashima
中科院分区：
文献类型：
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作者：
T. Yamashima
长链多不饱和脂肪酸(PUFA)，如二十二碳六烯酸和花生四烯酸，富含在大脑中，对神经元发育和功能的多个方面都具有重要作用，包括轴突生长、信号转导和膜流动性。最近的研究表明，多不饱和脂肪酸能够改善海马长时程增强、老年大鼠的学习能力和记忆缺陷人类的认知功能，但其潜在机制尚不清楚。已有一些研究G蛋白偶联受体40(GPR40)在胰腺中的生理作用的报道，但还没有关于GPR40在脑中的功能的研究。由于最近在整个大脑的神经元中发现了GPR40，很可能某些多不饱和脂肪酸可能作为内源性配体作用于GPR40的细胞表面。然而，多不饱和脂肪酸对神经元功能的影响仍不清楚。这里，虽然是周向的，但结合体外和体内的数据来考虑二十二碳六烯酸和花生四烯酸对大脑功能的影响。GPR40存在于成年猕猴正常和缺血后新生的海马神经元中，而PUFA对转GPR40基因的PC12细胞和记忆障碍者的钙动员和认知功能都有积极的影响。本综述的目的是通过讨论PUFA是否能通过激活GPR40来改善成年神经元的记忆功能，从而提出PUFA、GPR40和海马神经元之间的可能联系。目前，人们对多不饱和脂肪酸对成年海马区神经发生的需求知之甚少。然而，“PUFA-GPR40相互作用可能对成人神经发生和/或记忆至关重要”这一观点应该使用各种实验范式进行详细检验。
Long chain polyunsaturated fatty acids (PUFA) such as docosahexaenoic and arachidonic acids, which are enriched in the brain, are important for multiple aspects of neuronal development and function including neurite outgrowth, signal transduction and membrane fluidity. Recent studies show that PUFA are capable of improving hippocampal long-term potentiation, learning ability of aged rats, and cognitive function of humans with memory deficits, although the underlying mechanisms are unknown. There have been several reports studying physiological roles of G-protein coupled receptor 40 (GPR40) in the pancreas, but no studies have focused on the function of GPR40 in the brain. As GPR40 was recently identified in neurons throughout the brain, it is probable that certain PUFA may act, as endogenous ligands, on GPR40 at their cell surface. However, the effects of PUFA upon neuronal functions are still not clearly understood. Here, although circumferential, a combination of in vitro and in vivo data is introduced to consider the effects of docosahexaenoic and arachidonic acids on brain functions. GPR40 was found in the newborn neurons of the normal and postischemic hippocampi of adult macaque monkeys, while the positive effects of PUFA upon Ca2+mobilization and cognitive functions were demonstrated in both GPR40 gene-transfected PC12 cells and human subjects with memory deficits. The purpose of this review is to propose a putative link among PUFA, GPR40, and hippocampal newborn neurons by discussing whether PUFA can improve memory functions through GPR40 activation of adult-born neurons. At present, little is known about PUFA requirements that make possible neurogenesis in the adult hippocampus. However, the idea that ‘PUFA–GPR40 interaction might be crucial for adult neurogenesis and/or memory’ should be examined in detail using various experimental paradigms.