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

TY - JOUR

T1 - Direct neuronal glucose uptake Heralds activity-dependent increases in cerebral metabolism

AU - Lundgaard, Iben

AU - Li, Baoman

AU - Xie, Lulu

AU - Kang, Hongyi

AU - Sanggaard, Simon

AU - Haswell, John D R

AU - Sun, Wei

AU - Goldman, Siri

AU - Blekot, Solomiya

AU - Nielsen, Michael

AU - Takano, Takahiro

AU - Deane, Rashid

AU - Nedergaard, Maiken

PY - 2015/4/23

Y1 - 2015/4/23

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms7807

DO - 10.1038/ncomms7807

M3 - Journal article

C2 - 25904018

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 6807

ER -