Regulation of neurite growth by spontaneous Ca2+ oscillations in astrocytes

Abstract

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 Ca2+ signal-deficient astrocytes in which spontaneous Ca2+ oscillations were abolished by a chronic inhibition of IP3 signaling. When hippocampal neurons were cultured on a monolayer of Ca2+ 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 Ca2+ 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 Ca2+ signal-deficient astrocytes. These findings suggest that spontaneous Ca2+ 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. Copyright © 2007 Society for Neuroscience.