Regulation of neurite growth by spontaneous Ca2+ oscillations in astrocytes

J Neurosci. 2007 Aug 15;27(33):8957-66. doi: 10.1523/JNEUROSCI.2276-07.2007.


Astrocytes play a pivotal role in the regulation of neurite growth, but the intracellular signaling mechanism in astrocytes that mediates this regulation remains unclarified. We studied the relationship between spontaneous Ca(2+) oscillations in astrocytes and the astrocyte-mediated neurite growth. We generated Ca(2+) signal-deficient astrocytes in which spontaneous Ca(2+) oscillations were abolished by a chronic inhibition of IP(3) signaling. When hippocampal neurons were cultured on a monolayer of Ca(2+) signal-deficient astrocytes, the growth of dendrites and axons was inhibited. Time-lapse imaging of the advancement of axonal growth cones indicated the involvement of membrane-bound molecules for this inhibition. Among six candidate membrane-bound molecules that may modulate neuronal growth, N-cadherin was downregulated in Ca(2+) signal-deficient astrocytes. Although a blocking antibody to N-cadherin suppressed the axonal growth on control astrocytes, extrinsic N-cadherin expression rescued the suppressed axonal growth on Ca(2+) signal-deficient astrocytes. These findings suggest that spontaneous Ca(2+) oscillations regulate the astrocytic function to promote neurite growth by maintaining the expression of specific growth-enhancing proteins on their surface, and that N-cadherin is one of such molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Cells, Cultured
  • Coculture Techniques / methods
  • Drug Interactions
  • Embryo, Mammalian
  • Enzyme Inhibitors / pharmacology
  • Glial Fibrillary Acidic Protein / metabolism
  • Growth Cones / drug effects
  • Growth Cones / physiology
  • Hippocampus / cytology
  • Inositol Polyphosphate 5-Phosphatases
  • Mutation / physiology
  • Neurites / physiology*
  • Neurons / cytology*
  • Neurons / drug effects
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Thapsigargin / pharmacology
  • Transfection / methods
  • Tubulin / metabolism


  • Enzyme Inhibitors
  • Glial Fibrillary Acidic Protein
  • Tubb3 protein, rat
  • Tubulin
  • Thapsigargin
  • Phosphoric Monoester Hydrolases
  • Inositol Polyphosphate 5-Phosphatases
  • Calcium