Du Fei, Zhu Xiao-Hong, Zhang Yi, Friedman Michael, Zhang Nanyin, Ugurbil Kâmil, Chen Wei
Department of Radiology, Center for Magnetic Resonance Research and Department of Biomedical Engineering, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6409-14. doi: 10.1073/pnas.0710766105. Epub 2008 Apr 28.
A majority of ATP in the brain is formed in the mitochondria through oxidative phosphorylation of ADP with the F(1)F(0)-ATP (ATPase) enzyme. This ATP production rate plays central roles in brain bioenergetics, function and neurodegeneration. In vivo (31)P magnetic resonance spectroscopy combined with magnetization transfer (MT) is the sole approach able to noninvasively determine this ATP metabolic rate via measuring the forward ATPase reaction flux (F(f,ATPase)). However, previous studies indicate lack of quantitative agreement between F(f,ATPase) and oxidative metabolic rate in heart and liver. In contrast, recent work has shown that F(f,ATPase) might reflect oxidative phosphorylation rate in resting human brains. We have conducted an animal study, using rats under varied brain activity levels from light anesthesia to isoelectric state, to examine whether the in vivo (31)P MT approach is suitable for measuring the oxidative phosphorylation rate and its change associated with varied brain activity. Our results conclude that the measured F(f,ATPase) reflects the oxidative phosphorylation rate in resting rat brains, that this flux is tightly correlated to the change of energy demand under varied brain activity levels, and that a significant amount of ATP energy is required for "housekeeping" under the isoelectric state. These findings reveal distinguishable characteristics of ATP metabolism between the brain and heart, and they highlight the importance of in vivo (31)P MT approach to potentially provide a unique and powerful neuroimaging modality for noninvasively studying the cerebral ATP metabolic network and its central role in bioenergetics associated with brain function, activation, and diseases.
大脑中的大部分ATP是通过F(1)F(0)-ATP（ATP酶）将ADP氧化磷酸化在线粒体中形成的。这种ATP生成速率在大脑生物能量学、功能及神经退行性变中起着核心作用。体内磷磁共振波谱结合磁化传递（MT）是唯一能够通过测量正向ATP酶反应通量（F(f,ATPase)）非侵入性地确定这种ATP代谢速率的方法。然而，先前的研究表明F(f,ATPase)与心脏和肝脏中的氧化代谢速率缺乏定量一致性。相比之下，最近的研究表明F(f,ATPase)可能反映静息人类大脑中的氧化磷酸化速率。我们进行了一项动物研究，使用处于从轻度麻醉到等电状态的不同大脑活动水平的大鼠，以检验体内磷MT方法是否适用于测量氧化磷酸化速率及其与不同大脑活动相关的变化。我们的结果得出结论，所测得的F(f,ATPase)反映了静息大鼠大脑中的氧化磷酸化速率，该通量与不同大脑活动水平下能量需求的变化紧密相关，并且在等电状态下“维持基本功能”需要大量的ATP能量。这些发现揭示了大脑和心脏之间ATP代谢的显著特征，并突出了体内磷MT方法的重要性，该方法有可能提供一种独特且强大的神经成像方式，用于非侵入性地研究大脑ATP代谢网络及其在与脑功能、激活和疾病相关的生物能量学中的核心作用。
