Lactate rescues neuronal sodium homeostasis during impaired energy metabolism

Channels (Austin). 2015;9(4):200-8. doi: 10.1080/19336950.2015.1050163. Epub 2015 Jun 3.


Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle.

Keywords: astrocytes; energy deprivation; glycolysis; hippocampus; lactate shuttle; metabolism; neuron-glia interaction; sodium oscillations; tricarboxylic acid cycle.

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Energy Metabolism / drug effects*
  • Female
  • Glucose / pharmacology
  • Glutamic Acid / pharmacology
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Homeostasis / drug effects*
  • Lactates / pharmacology*
  • Male
  • Mice, Inbred BALB C
  • Neuroglia / metabolism
  • Neurons / metabolism*
  • Signal Transduction / drug effects
  • Sodium / metabolism*


  • Lactates
  • Glutamic Acid
  • Sodium
  • Glucose