Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences-Wuhan National Laboratory for Optoelectronics, Wuhan, Hubei, 430071, People's Republic of China.
Mol Neurobiol. 2024 Aug;61(8):5802-5813. doi: 10.1007/s12035-024-03927-w. Epub 2024 Jan 17.
Lactate is not only the energy substrate of neural cells, but also an important signal molecule in brain. In modern societies, disturbed circadian rhythms pose a global challenge. Therefore, exploring the influence of circadian period on lactate and its metabolic kinetics is essential for the advancement of neuroscientific research. In the present study, the different groups of mice (L: 8:00 a.m.; D: 20:00 p.m.; SD: 20:00 p.m. with 12 h acute sleep deprivation) were infused with [3-C] lactate through the lateral tail vein for a duration of 2 min. After 30-min lactate metabolism, the animals were euthanized and the tissues of brain and liver were obtained and extracted, and then, the [H-C] NMR technology was employed to investigate the kinetic information of lactate metabolism in different brain regions and liver to detect the enrichment of various metabolic kinetic information. Results revealed the fluctuating lactate concentrations in the brain throughout the day, with lower levels during light periods and higher levels during dark periods. Most metabolites displayed strong sensitivity to circadian rhythm, exhibiting significant day-night variations. Conversely, only a few metabolites showed changes after acute sleep deprivation, primarily in the temporal brain region. Interestingly, in contrast to brain lactate metabolism, liver lactate metabolism exhibited a significant increase following acute sleep deprivation. This study explored the kinetics of lactate metabolism, hinted at potential clinical implications for disorders involving circadian rhythm disturbances, and providing a new research basis for clinical exploration of brain and liver lactate metabolism.
乳酸不仅是神经细胞的能量底物,还是脑内的重要信号分子。在现代社会中,紊乱的昼夜节律构成了全球性挑战。因此,探索昼夜周期对乳酸及其代谢动力学的影响,对于推进神经科学研究至关重要。在本研究中,通过尾静脉侧注入[3-C]乳酸,对不同组别的小鼠(L:上午 8 点;D:晚上 8 点;SD:晚上 8 点并进行 12 小时急性睡眠剥夺)进行 2 分钟的输注。在 30 分钟的乳酸代谢后,处死动物并获取和提取脑组织和肝脏组织,然后利用[H-C]NMR 技术研究不同脑区和肝脏中乳酸代谢的动力学信息,以检测各种代谢动力学信息的富集情况。结果揭示了大脑中乳酸浓度全天呈波动变化,在光照期较低,在暗期较高。大多数代谢物对昼夜节律具有很强的敏感性,表现出明显的昼夜变化。相反,急性睡眠剥夺后仅少数代谢物发生变化,主要发生在颞叶脑区。有趣的是,与脑乳酸代谢不同,急性睡眠剥夺后肝脏乳酸代谢显著增加。本研究探索了乳酸代谢的动力学,暗示了昼夜节律紊乱相关疾病的潜在临床意义,并为脑和肝脏乳酸代谢的临床探索提供了新的研究基础。