Endogenous activation of metabotropic glutamate receptors supports the proliferation and survival of neural progenitor cells

Cell Death Differ. 2005 Aug;12(8):1124-33. doi: 10.1038/sj.cdd.4401639.

Abstract

The use of neural progenitor cells (NPCs) is limited by the incomplete knowledge of the extracellular signals regulating their proliferation and survival. We report that cultured mouse NPCs express functional mGlu3 and mGlu5 metabotropic glutamate receptors. Pharmacological blockade of both receptors reduced NPC proliferation and survival, whereas activation of mGlu5 receptors substantially enhanced cell proliferation. Adult mice lacking mGlu5 receptors or treated with mGlu5 or mGlu3 receptor antagonists showed a dramatic reduction in the number of dividing neuroprogenitors present in the subventricular zone and in the dentate gyrus of the hippocampus. These data disclose a novel function of mGlu receptors and offer new potential strategies for the optimization of cell replacement therapy in neurodegenerative disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Cycle / physiology
  • Cell Growth Processes / physiology
  • Cell Survival / drug effects
  • Cells, Cultured
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • Neurons / cytology*
  • Neurons / metabolism
  • Prosencephalon / cytology
  • Prosencephalon / metabolism
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / metabolism
  • Receptors, Metabotropic Glutamate / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / cytology*
  • Stem Cells / metabolism

Substances

  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 3

Grant support