Astrocyte-neuron crosstalk regulates the expression and subcellular localization of carbohydrate metabolism enzymes

Glia. 2015 Feb;63(2):328-40. doi: 10.1002/glia.22753. Epub 2014 Sep 24.

Abstract

Astrocytes releasing glucose- and/or glycogen-derived lactate and glutamine play a crucial role in shaping neuronal function and plasticity. Little is known, however, how metabolic functions of astrocytes, e.g., their ability to degrade glucosyl units, are affected by the presence of neurons. To address this issue we carried out experiments which demonstrated that co-culturing of rat hippocampal astrocytes with neurons significantly elevates the level of mRNA and protein for crucial enzymes of glycolysis (phosphofructokinase, aldolase, and pyruvate kinase), glycogen metabolism (glycogen synthase and glycogen phosphorylase), and glutamine synthetase in astrocytes. Simultaneously, the decrease of the capability of neurons to metabolize glucose and glutamine is observed. We provide evidence that neurons alter the expression of astrocytic enzymes by secretion of as yet unknown molecule(s) into the extracellular fluid. Moreover, our data demonstrate that almost all studied enzymes may localize in astrocytic nuclei and this localization is affected by the co-culturing with neurons which also reduces proliferative activity of astrocytes. Our results provide the first experimental evidence that the astrocyte-neuron crosstalk substantially affects the expression of basal metabolic enzymes in the both types of cells and influences their subcellular localization in astrocytes.

Keywords: glutamine synthetase; glycogen; glycolysis; nuclear localization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Animals, Newborn
  • Astrocytes / cytology*
  • Carbohydrate Metabolism / physiology*
  • Cells, Cultured
  • Coculture Techniques
  • Culture Media, Conditioned / pharmacology
  • Fructose-Bisphosphate Aldolase / metabolism
  • Glycogen Synthase / metabolism
  • Hippocampus / cytology
  • Neurons / chemistry
  • Neurons / cytology*
  • Proteomics
  • Pyruvate Kinase / metabolism
  • Rats
  • Rats, Wistar
  • Subcellular Fractions / enzymology*

Substances

  • Actins
  • Culture Media, Conditioned
  • Glycogen Synthase
  • Pyruvate Kinase
  • Fructose-Bisphosphate Aldolase