乳酸影响记忆的神经机制

The Neural Mechanism of Lactate Affecting Memory

乳酸在以往的研究中一直被认为是糖酵解的产物,是不受欢迎的代谢副产品。近30年的研究证明乳酸可以作为能量底物,也可以通过影响信号通路影响神经活动。乳酸对空间记忆、恐惧记忆,成瘾记忆均能够发挥作用。星形胶质细胞和少突胶质细胞中产生的乳酸,转运到神经元中为神经元提供能量进而影响记忆。乳酸可以直接作用于乳酸受体,也可以间接通过促进神经发生、增强N-甲基-D-天冬氨酸受体(N-methyl-D-aspartic acid receptor,NMDAR)的活性促进突触可塑性和即刻早期基因的表达、诱导脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)的表达进而影响记忆。乳酸还是与记忆有关的神经系统性疾病的潜在治疗靶点,例如阿尔茨海默病(Alzheimer’s disease,AD)。本文综述了乳酸产生对不同记忆的影响、不同神经递质调控乳酸的产生对记忆的影响、乳酸影响记忆的神经机制、乳酸在与记忆有关神经性退行疾病中的作用。通过上述方面的梳理,希望进一步为乳酸在记忆中作用和乳酸在神经系统中作用的研究提供新的思路。

In the past studies,lactate has been regarded as a product of glycolysis,namely an undesirable metabolic by-product.In recent 30 years,studies have proved that lactate can be used as an energy substrate,and it can also participate in neural activity by affecting signal pathways.Lactate can play a role in spatial memory,fear memory and addiction memory.Lactate generated in astrocytes and oligodendrocytes is transported to neurons,so as to provide energy for neurons and affect memory.Lactate can not only directly act on lactate receptor,but also indirectly promote neurogenesis,synaptic plasticity and immediate early gene expression by enhancing the activity of N-methyl-D-aspartic acid receptor,and induce the expression of brain-derived neurotrophic factor,thus affecting memory.Lactate is also a potential therapeutic target for neurological diseases related to memory,such as Alzheimer's disease.This paper reviews the effects of lactate production on different memory,the effects of different neurotransmitters regulating lactate production on memory,the neural mechanism of lactate affecting memory,and the role of lactate in neurodegenerative diseases related to memory.Through combing the above aspects,it is hoped to further provide new ideas for the study on the role of lactate in memory and the role of lactate in nervous system.