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The CNS consumes tenfold more energy than the average of peripheral tissue and relies almost exclusively on glucose as energy substrate. According to the astrocyte–to-neuron lactate shuttle hypothesis, glucose uptake is delegated to astrocytes and neurons rely chiefly on import of lactate from nearby astrocytes. The concept of the astrocyte-to-neuron lactate shuttle was originally based on the observation that glutamate uptake in cultured astrocytes activated aerobic glycolysis, leading to an increased astrocytic production of lactate8. Accordingly, glutamatergic signalling enhances astrocytic lactate production and lactate is in turn imported and oxidized by neurons. Several experiments have in the past supported the existence of astrocyte-to-neuron lactate shuttle hypothesis.
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