Lactate shuttle · Grey Matter

The lactate shuttle is the proposal that astrocytes break down glucose to lactate during activity and pass it to neurons as fuel, coupling the synaptic work an astrocyte sees to the energy a neuron receives; it is an influential and still contested model of how brain cells share their energy.

Lactate shuttle. The lactate shuttle is the proposal that astrocytes break down glucose to lactate during activity and pass it to neurons as fuel, coupling the synaptic work an astrocyte sees to the energy a neuron receives; it is an influential and still contested model of how brain cells share their energy.

The astrocyte-neuron lactate shuttle was proposed by Pellerin and Magistretti in 1994. In its original form, glutamate released at a synapse is taken up by an astrocyte together with sodium; the extra sodium has to be pumped out, the pump consumes ATP, and the astrocyte answers by speeding up glycolysis, exporting the resulting lactate. Neurons take the lactate up, convert it to pyruvate and oxidise it in their mitochondria. Astrocytes also store the brain's only significant fuel reserve, glycogen, which can be broken down to lactate in the same way.

Lactate does move between cells. Transporters for it (monocarboxylate transporters) are expressed on both cell types, and astrocytic lactate supports some forms of memory consolidation in animal studies.

The size of its energetic role is disputed. Measurements show that neurons also take up and phosphorylate glucose directly during activity, and calculations of the fluxes argue that the shuttle cannot supply most of neuronal energy; other work supports a larger role.

Lactate may also signal. Beyond fuel, it acts on receptors and on gene expression, so its effects need not track its contribution to ATP.

The shuttle asks who feeds the neuron during work.

Its answer, partly the astrocyte, is plausible and partly supported, but how much of a neuron's fuel arrives this way is still an open question.

Questions: Do astrocytes feed neurons with lactate? Partly, and how much is debated. Pellerin and Magistretti proposed in 1994 that glutamate uptake makes astrocytes speed up glycolysis and export lactate, which neurons then oxidise, a neat link between synaptic activity and fuel delivery. Lactate transporters on both cells and animal studies in which astrocytic lactate supports memory consolidation back a role for it. Critics point out that neurons also take up and use glucose directly during activity, and that the measured fluxes do not add up to astrocytes supplying most neuronal energy, so the shuttle is best treated as a real but contested contribution.