Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia

J Cereb Blood Flow Metab. 2014 Jun;34(6):945-55. doi: 10.1038/jcbfm.2014.33. Epub 2014 Feb 26.


Glycogen is present in the brain, where it has been found mainly in glial cells but not in neurons. Therefore, all physiologic roles of brain glycogen have been attributed exclusively to astrocytic glycogen. Working with primary cultured neurons, as well as with genetically modified mice and flies, here we report that-against general belief-neurons contain a low but measurable amount of glycogen. Moreover, we also show that these cells express the brain isoform of glycogen phosphorylase, allowing glycogen to be fully metabolized. Most importantly, we show an active neuronal glycogen metabolism that protects cultured neurons from hypoxia-induced death and flies from hypoxia-induced stupor. Our findings change the current view of the role of glycogen in the brain and reveal that endogenous neuronal glycogen metabolism participates in the neuronal tolerance to hypoxic stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Hypoxia / genetics
  • Cells, Cultured
  • Gene Expression Regulation, Enzymologic / genetics
  • Glycogen / genetics
  • Glycogen / metabolism*
  • Glycogen Phosphorylase, Brain Form / biosynthesis
  • Glycogen Phosphorylase, Brain Form / genetics
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Neurons / cytology
  • Neurons / metabolism*


  • Nerve Tissue Proteins
  • Glycogen
  • Glycogen Phosphorylase, Brain Form