Matsui Takashi, Liu Yu-Fan, Soya Mariko, Shima Takeru, Soya Hideaki
Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, Japan.
Sport Neuroscience Division, Advanced Research Initiative for Human High Performance (ARIHHP), University of Tsukuba, Tsukuba, Japan.
Front Neurosci. 2019 Mar 19;13:200. doi: 10.3389/fnins.2019.00200. eCollection 2019.
Brain glycogen, localized in astrocytes, produces lactate as an energy source and/or a signal factor to serve neuronal functions involved in memory formation and exercise endurance. In rodents, 4 weeks of chronic moderate exercise-enhancing endurance and cognition increases brain glycogen in the hippocampus and cortex, which is an adaption of brain metabolism achieved through exercise. Although this brain adaptation is likely induced due to the accumulation of acute endurance exercise-induced brain glycogen supercompensation, its molecular mechanisms and biomarkers are unidentified. Since noradrenaline synthesized from blood-borne tyrosine activates not only glycogenolysis but also glycogenesis in astrocytes, we hypothesized that blood tyrosine is a mechanistic-based biomarker of acute exercise-induced brain glycogen supercompensation. To test this hypothesis, we used a rat model of endurance exercise, a microwave irradiation for accurate detection of glycogen in the brain (the cortex, hippocampus, and hypothalamus), and capillary electrophoresis mass spectrometry-based metabolomics to observe the comprehensive metabolic profile of the blood. Endurance exercise induced fatigue factors such as a decrease in blood glucose, an increase in blood lactate, and the depletion of muscle glycogen, but those parameters recovered to basal levels within 6 h after exercise. Brain glycogen decreased during endurance exercise and showed supercompensation within 6 h after exercise. Metabolomics detected 186 metabolites in the plasma, and 110 metabolites changed significantly during and following exhaustive exercise. Brain glycogen levels correlated negatively with plasma glycogenic amino acids (serine, proline, threonine, glutamate, methionine, tyrosine, and tryptophan) ( < -0.9). This is the first study to produce a broad picture of plasma metabolite changes due to endurance exercise-induced brain glycogen supercompensation. Our findings suggest that plasma glycogenic amino acids are sensitive indicators of brain glycogen levels in endurance exercise. In particular, plasma tyrosine as a precursor of brain noradrenaline might be a valuable mechanistic-based biomarker to predict brain glycogen dynamics in endurance exercise.
脑糖原存在于星形胶质细胞中，可产生乳酸作为能量来源和/或信号因子，以支持与记忆形成和运动耐力相关的神经元功能。在啮齿动物中，为期4周的慢性适度运动可增强耐力和认知能力，增加海马体和皮质中的脑糖原，这是通过运动实现的脑代谢适应。尽管这种脑适应可能是由于急性耐力运动诱导的脑糖原超补偿积累所致，但其分子机制和生物标志物尚未明确。由于由血液中的酪氨酸合成的去甲肾上腺素不仅能激活星形胶质细胞中的糖原分解，还能激活糖原合成，我们推测血液中的酪氨酸是急性运动诱导的脑糖原超补偿的基于机制的生物标志物。为了验证这一假设，我们使用了耐力运动大鼠模型、用于精确检测脑内（皮质、海马体和下丘脑）糖原的微波辐射，以及基于毛细管电泳质谱的代谢组学技术来观察血液的综合代谢谱。耐力运动诱导了疲劳因子，如血糖降低、血乳酸增加和肌肉糖原消耗，但这些参数在运动后6小时内恢复到基础水平。脑糖原在耐力运动期间减少，并在运动后6小时内出现超补偿。代谢组学检测到血浆中有186种代谢物，其中110种代谢物在力竭运动期间及之后发生了显著变化。脑糖原水平与血浆生糖氨基酸（丝氨酸、脯氨酸、苏氨酸、谷氨酸、蛋氨酸、酪氨酸和色氨酸）呈负相关（< -0.9）。这是第一项全面描绘耐力运动诱导的脑糖原超补偿导致的血浆代谢物变化的研究。我们的研究结果表明，血浆生糖氨基酸是耐力运动中脑糖原水平的敏感指标。特别是，作为脑去甲肾上腺素前体的血浆酪氨酸可能是预测耐力运动中脑糖原动态变化的有价值的基于机制的生物标志物。
