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Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism

Nature Communications volume 6, Article number: 6807 (2015) | Download Citation

Abstract

Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using two-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anaesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover, hexokinase, which catalyses the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identiy the neuron as the principal locus of glucose uptake as visualized by functional brain imaging.

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Acknowledgements

This work was supported by the Novo Nordisk Foundation, NIH/NINDS and the Lundbeck Foundation. We thank Weiguo Peng, Yonghong Liao and Thiyagarajan Meenakshisundaram for expert technical assistance. GLT1-eGFP mice were kindly donated by Jeff Rothstein.

Author information

Author notes

    • Iben Lundgaard
    • , Baoman Li
    •  & Lulu Xie

    These authors contributed equally to this work

Affiliations

  1. Center for Translational Neuromedicine, University of Rochester, Rochester, New York 14642, USA

    • Iben Lundgaard
    • , Baoman Li
    • , Lulu Xie
    • , Hongyi Kang
    • , Simon Sanggaard
    • , John D. R. Haswell
    • , Wei Sun
    • , Siri Goldman
    • , Solomiya Blekot
    • , Michael Nielsen
    • , Takahiro Takano
    • , Rashid Deane
    •  & Maiken Nedergaard
  2. Faculty of Health and Medical Sciences, Center for Basic and Translational Neuroscience, University of Copenhagen, DK-2200 Copenhagen N, Denmark

    • Iben Lundgaard
    • , Lulu Xie
    • , Hongyi Kang
    • , Simon Sanggaard
    • , John D. R. Haswell
    • , Wei Sun
    • , Siri Goldman
    • , Solomiya Blekot
    • , Michael Nielsen
    • , Takahiro Takano
    • , Rashid Deane
    •  & Maiken Nedergaard
  3. Department of Clinical Pharmacology, China Medical University, 110001 Shenyang, China

    • Baoman Li

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Contributions

I.L., L.X., B.L., R.D. and M.N. designed and interpreted experiments, and wrote the manuscript. I.L., L.X., B.L., R.D., H.K., S.S., J.D.R.H., W.S., S.G., S.B., M.H. and T.T. performed experiments and analysed data.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Iben Lundgaard or Maiken Nedergaard.

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DOI

https://doi.org/10.1038/ncomms7807

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