GABA suppresses neurogenesis in the adult hippocampus through GABAB receptors

Development. 2014 Jan;141(1):83-90. doi: 10.1242/dev.102608. Epub 2013 Nov 27.

Abstract

Adult neurogenesis is tightly regulated through the interaction of neural stem/progenitor cells (NSCs) with their niche. Neurotransmitters, including GABA activation of GABAA receptor ion channels, are important niche signals. We show that adult mouse hippocampal NSCs and their progeny express metabotropic GABAB receptors. Pharmacological inhibition of GABAB receptors stimulated NSC proliferation and genetic deletion of GABAB1 receptor subunits increased NSC proliferation and differentiation of neuroblasts in vivo. Cell-specific conditional deletion of GABAB receptors supports a cell-autonomous role in newly generated cells. Our data indicate that signaling through GABAB receptors is an inhibitor of adult neurogenesis.

Keywords: GABAB receptors; Mouse; Neural stem cells; Neurotransmitters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation / drug effects
  • Cell Survival / genetics
  • GABA-B Receptor Antagonists / pharmacology
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Mice
  • Mice, Knockout
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism*
  • Neurogenesis / drug effects
  • Neurogenesis / genetics
  • Neurogenesis / physiology*
  • Neurons / cytology
  • Neurons / metabolism
  • Organophosphorus Compounds / pharmacology
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism
  • Receptors, GABA-B / genetics
  • Receptors, GABA-B / metabolism*
  • Signal Transduction / physiology
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • GABA-B Receptor Antagonists
  • Organophosphorus Compounds
  • Receptors, GABA-A
  • Receptors, GABA-B
  • CGP 54626
  • gamma-Aminobutyric Acid