Tightly coupled brain activity and cerebral ATP metabolic rate. Proc Natl Acad Sci USA

Department of Radiology, Center for Magnetic Resonance Research and Department of Biomedical Engineering, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 05/2008; 105(17):6409-14. DOI: 10.1073/pnas.0710766105
Source: PubMed


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.

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Available from: Fei Du, Jan 12, 2015
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    • "In contrast, after the induction of anesthesia brain oxygen and glucose consumption are reduced by ∼40–50% as revealed by PET measurements; these values decline further to ∼15–20% of baseline upon reaching deeper levels of anesthesia with pentobarbital (Shulman et al., 2009). Similarly , results from 31P magnetic resonance spectroscopy (MRS) studies, combined with magnetization transfer method to measure the rate of P inorganic conversion to ATP, determined that the progressive decline of ATP metabolism with increasing levels of anesthesia was parallel to the decline in brain EEG activity; at an isoelectric state the oxidative production rate of ATP was reduced to 50% compared to light isoflurane anesthesia condition (Du et al., 2008). Thus, the conscious state provides a baseline for activation but also represents a high level of spontaneous neural activity and accompanying metabolic demand, which can be substantially reduced with progressively deeper general anesthesia. "
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