Can lactate serve as an energy substrate for axons in good times and in bad, in sickness and in health?
- 665 Downloads
In the mammalian white matter, glycogen-derived lactate from astrocytes plays a critical role in supporting axon function using the astrocyte-neuron lactate transfer shuttle (ANLTS) system with specialized monocarboxylate transporters (MCTs). A rapid breakdown of glycogen to lactate during increased neuronal activity or low glucose conditions becomes essential to maintain axon function. Therefore astrocytes actively regulate their glycogen stores with respect to ambient glucose levels such that high ambient glucose upregulates glycogen and low levels of glucose depletes glycogen stores. Although lactate fully supports axon function in the absence of glucose and becomes a preferred energy metabolite when axons discharge at high frequency, it fails to benefit axon function during an ischemic episode in white matter. Emerging evidence implies a similar lactate transport system between oligodendrocytes and the axons they myelinate, suggesting another metabolic coupling pathway in white matter. Therefore the conditions that activate this lactate shuttle system and the signaling mechanisms that mediate activation of this system are of great interest. Future studies are expected to unravel the details of oligodendrocyte-axon lactate metabolic coupling to establish how white matter components metabolically cooperate and that lactate may be the universal metabolite to sustain CNS function.
KeywordsD-lactate White matter Axon Oligodendrocytes End-feet
This work was supported by grants from the American Stroke Association and the National Institute of Aging (NIA) to SB, as well as a gift from Rose Mary Kubik. Selva Baltan has previously published as Selva Tekkök.
- Amaral AI, Meisingset TW, Kotter MR, Sonnewald U (2013) Metabolic aspects of neuron-oligodendrocyte-astrocyte interactions. Front Endocrinol (Lausanne) 4:54Google Scholar
- Broer S, Rahman B, Pellegri G, Pellerin L, Martin JL, Verleysdonk S, Hamprecht B, Magistretti PJ (1997) Comparison of lactate transport in astroglial cells and monocarboxylate transporter 1 (MCT 1) expressing Xenopus laevis oocytes. Expression of two different monocarboxylate transporters in astroglial cells and neurons. J Biol Chem 272:30096–30102PubMedCrossRefGoogle Scholar
- Frier BM, Fisher BM (1999) Hypoglycemia in clinical diabetes. Wiley, New YorkGoogle Scholar
- Funfschilling U, Supplie LM, Mahad D, Boretius S, Saab AS, Edgar J, Brinkmann BG, Kassmann CM, Tzvetanova ID, Mobius W, Diaz F, Meijer D, Suter U, Hamprecht B, Sereda MW, Moraes CT, Frahm J, Goebbels S, Nave KA (2012) Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature 485:517–521PubMedCentralPubMedGoogle Scholar