Acute feedback control of astrocytic glycolysis by lactate
Glia. 2012-01-30; 60(4): 674-680
DOI: 10.1002/glia.22304
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Neuronal activity is accompanied by a rapid increase in interstitial lactate,
which is hypothesized to serve as a fuel for neurons and a signal for local
vasodilation. Using FRET microscopy, we report here that the rate of glycolysis
in cultured mice astrocytes can be acutely modulated by physiological changes in
extracellular lactate. Glycolytic inhibition by lactate was not accompanied by
detectable variations in intracellular pH or intracellular ATP and was not
dependent of mitochondrial function. Pyruvate was also inhibitory, suggesting
that the effect of lactate is not mediated by the NADH/NAD(+) ratio. We propose
that lactate serves as a fast negative feedback signal limiting its own
production by astrocytes and therefore the amplitude of the lactate surge. The
inhibition of glucose usage by lactate was much stronger in resting astrocytes
than in K(+)-stimulated astrocytes, which suggests that lactate may also help
diverting glucose from resting to active zones.