Tightly coupled brain activity and cerebral ATP metabolic rate

Fei Du, Xiao Hong Zhu, Yi Zhang, Michael Friedman, Nanyin Zhang, Kâmil Uǧurbil, Wei Chen

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

A majority of ATP in the brain is formed in the mitochondria through oxidative phosphorylation of ADP with the F1F0-ATP (ATPase) enzyme. This ATP production rate plays central roles in brain bioenergetics, function and neurodegeneration. In vivo 31P 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 (Ff,ATPase). However, previous studies indicate lack of quantitative agreement between Ff,ATPase and oxidative metabolic rate in heart and liver. In contrast, recent work has shown that Ff,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 31PMT approach is suitable for measuring the oxidative phosphorylation rate and its change associated with varied brain activity. Our results conclude that the measured Ff,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 31P 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.

Original languageEnglish (US)
Pages (from-to)6409-6414
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number17
DOIs
StatePublished - Apr 29 2008

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Adenosine Triphosphate
Adenosine Triphosphatases
Brain
Oxidative Phosphorylation
Energy Metabolism
Housekeeping
Metabolic Networks and Pathways
Neuroimaging
Adenosine Diphosphate
Mitochondria
Magnetic Resonance Spectroscopy
Anesthesia
Heart Rate
Liver
Enzymes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Du, Fei ; Zhu, Xiao Hong ; Zhang, Yi ; Friedman, Michael ; Zhang, Nanyin ; Uǧurbil, Kâmil ; Chen, Wei. / Tightly coupled brain activity and cerebral ATP metabolic rate. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 17. pp. 6409-6414.
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Tightly coupled brain activity and cerebral ATP metabolic rate. / Du, Fei; Zhu, Xiao Hong; Zhang, Yi; Friedman, Michael; Zhang, Nanyin; Uǧurbil, Kâmil; Chen, Wei.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 17, 29.04.2008, p. 6409-6414.

Research output: Contribution to journalArticle

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AU - Du, Fei

AU - Zhu, Xiao Hong

AU - Zhang, Yi

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