乳酸在中枢神经系统中的作用及其与相关疾病的关系

The Role of Lactate in the Central Nervous System and Its Relationship with Related Diseases

一直以来,乳酸在脑中被视作代谢废物,对其功能认识严重滞后。近年来,越来越多的证据表明,乳酸在多种生理与病理过程中扮演重要角色。在神经细胞中,星形胶质细胞是产生和释放乳酸的主要细胞源,该细胞通过有氧糖酵解过程生成乳酸,随后经跨膜通道释放至胞外进入神经元为其供能。在中枢神经系统中,乳酸对稳态调节发挥着十分重要的作用。乳酸主要通过两种途径,即代谢途径(作为能量底物)与信号途径(作为信号分子)调控神经元的功能活动,广泛参与神经元能量代谢、兴奋性、可塑性、学习记忆及神经系统发育等生理过程调节,亦参与抑郁行为、阿尔兹海默病(AD)和脑损伤等病理过程的调节。在脑组织中,存在着乳酸特异性受体(GPR81),乳酸与其结合后调控胞内的第二信使。此外,还发现乳酸可通过未知受体调节神经元的兴奋性以及作为信号分子的其他作用。本文就乳酸作为能量底物和信号分子及其参与相关神经疾病的研究进展进行阐述,旨在为相关中枢神经系统疾病防治提供新思路。

Lactate has always been regarded as a metabolic waste in the brain,and the understanding of its functions have been seriously lagging behind.In recent years,more and more experimental evidence has shown that lactate plays an important role in a variety of physiological and pathological processes.Among nerve cells,astrocytes are the main source of cells for the production and release of lactate.The cells produce lactate through aerobic glycolysis,which is then released to the outside of the cells via transmembrane channels and enters neurons to supply energy.In the central nervous system,lactate plays a significant role in homeostasis regulation.Lactate regulates the functions and activities of neurons mainly through two pathways:metabolic pathways(as energy substrates)and signal pathways(as signal molecules),which is extensively manifested in the regulation of physiological processes such as neuronal energy metabolism,excitatory,plasticity,learning and memory,and nervous system development,as well as the pathological processes including depression,Alzheimer’s disease(AD)and brain injury.There is a lactate-specific receptor(GPR81)in brain tissue,and lactate binds to it to regulate the intracellular second messenger.In addition,it was also found that lactate can modulate the excitability of neurons through unknown receptors and other functions as signal molecules.Therefore,this article focus on the research progress of lactate as an energy substrate and signaling molecule and its involvement in related neurological diseases,which may provide new ideas for the prevention and treatment of related central nervous system diseases.