Lactate Metabolism, Signaling, and Function in Brain Development, Synaptic Plasticity, Angiogenesis, and Neurodegenerative Diseases.
Lactate Metabolism, Signaling, and Function in Brain Development, Synaptic Plasticity, Angiogenesis, and Neurodegenerative Diseases.
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脑发育、突触可塑性、血管生成和神经退行性疾病中的乳酸代谢、信号和功能。
DOI：
10.3390/ijms241713398
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发表时间：
2023-08-29
影响因子：
5.6
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中科院分区：
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神经组织需要一个巨大的代谢需求，尽管可以忽略不计的内在能量储存。因此，中枢神经系统（CNS）依赖于来自血液的代谢底物的持续流入。这一过程的中断可能导致神经功能受损，意识丧失，并在几分钟内昏迷。复杂的神经血管网络允许空间和时间上适当的代谢底物递送。乳酸盐是厌氧或有氧糖酵解的终产物，通过乳酸脱氢酶-5（LDH-5）从丙酮酸盐转化而来。虽然它在大脑中含量丰富，但传统上被认为是糖酵解的副产品或废物。然而，最近的证据表明，乳酸可能是一个重要的能量来源，以及大脑和星形胶质细胞（最丰富的神经胶质细胞）的代谢信号分子，在能量传递，储存，生产和利用中发挥着至关重要的作用。星形胶质细胞-神经元乳酸穿梭假说指出，乳酸一旦被星形胶质细胞释放到细胞外空间，就可以被神经元摄取和代谢。这篇综述着重于这一假设，突出乳酸在大脑中的新兴作用，特别强调其在发育，突触可塑性，血管生成和疾病中的作用。
Neural tissue requires a great metabolic demand despite negligible intrinsic energy stores. As a result, the central nervous system (CNS) depends upon a continuous influx of metabolic substrates from the blood. Disruption of this process can lead to impairment of neurological functions, loss of consciousness, and coma within minutes. Intricate neurovascular networks permit both spatially and temporally appropriate metabolic substrate delivery. Lactate is the end product of anaerobic or aerobic glycolysis, converted from pyruvate by lactate dehydrogenase-5 (LDH-5). Although abundant in the brain, it was traditionally considered a byproduct or waste of glycolysis. However, recent evidence indicates lactate may be an important energy source as well as a metabolic signaling molecule for the brain and astrocytes—the most abundant glial cell—playing a crucial role in energy delivery, storage, production, and utilization. The astrocyte–neuron lactate-shuttle hypothesis states that lactate, once released into the extracellular space by astrocytes, can be up-taken and metabolized by neurons. This review focuses on this hypothesis, highlighting lactate’s emerging role in the brain, with particular emphasis on its role during development, synaptic plasticity, angiogenesis, and disease.