Institute of Medical Science, Tokyo Medical University, Tokyo 160-8402, Japan.
Department of Molecular Preventive Medicine, Tokyo Medical University, Tokyo 160-8402, Japan.
Nutrients. 2019 Sep 20;11(10):2265. doi: 10.3390/nu11102265.
Cholinergic neurons in the central nervous system play a vital role in higher brain functions, such as learning and memory. Choline is essential for the synthesis of the neurotransmitter acetylcholine by cholinergic neurons. The synthesis and metabolism of acetylcholine are important mechanisms for regulating neuronal activity. Choline is a positively charged quaternary ammonium compound that requires transporters to pass through the plasma membrane. Currently, there are three groups of choline transporters with different characteristics, such as affinity for choline, tissue distribution, and sodium dependence. They include (I) polyspecific organic cation transporters (OCT1-3: SLC22A1-3) with a low affinity for choline, (II) high-affinity choline transporter 1 (CHT1: SLC5A7), and (III) choline transporter-like proteins (CTL1-5: SLC44A1-5). Brain microvascular endothelial cells, which comprise part of the blood-brain barrier, take up extracellular choline via intermediate-affinity choline transporter-like protein 1 (CTL1) and low-affinity CTL2 transporters. CTL2 is responsible for excreting a high concentration of choline taken up by the brain microvascular endothelial cells on the brain side of the blood-brain barrier. CTL2 is also highly expressed in mitochondria and may be involved in the oxidative pathway of choline metabolism. Therefore, CTL1- and CTL2-mediated choline transport to the brain through the blood-brain barrier plays an essential role in various functions of the central nervous system by acting as the rate-limiting step of cholinergic neuronal activity.
中枢神经系统中的胆碱能神经元在学习和记忆等高级脑功能中起着至关重要的作用。胆碱是胆碱能神经元合成神经递质乙酰胆碱所必需的。乙酰胆碱的合成和代谢是调节神经元活动的重要机制。胆碱是一种带正电荷的季铵化合物，需要转运体穿过质膜。目前，有三组具有不同特征的胆碱转运体，如对胆碱的亲和力、组织分布和对钠的依赖性。它们包括（I）对胆碱亲和力低的多特异性有机阳离子转运体（OCT1-3：SLC22A1-3）、（II）高亲和力胆碱转运体 1（CHT1：SLC5A7）和（III）胆碱转运体样蛋白（CTL1-5：SLC44A1-5）。脑微血管内皮细胞构成血脑屏障的一部分，通过中亲和力胆碱转运体样蛋白 1（CTL1）和低亲和力 CTL2 转运体摄取细胞外胆碱。CTL2 负责将血脑屏障脑侧脑微血管内皮细胞摄取的高浓度胆碱排出。CTL2 在线粒体中也高度表达，可能参与胆碱代谢的氧化途径。因此，CTL1 和 CTL2 介导的通过血脑屏障向脑内转运胆碱，通过作为胆碱能神经元活动的限速步骤，对中枢神经系统的各种功能起着至关重要的作用。
