Opposing effects of α2- and β-adrenergic receptor stimulation on quiescent neural precursor cell activity and adult hippocampal neurogenesis

PLoS One. 2014 Jun 12;9(6):e98736. doi: 10.1371/journal.pone.0098736. eCollection 2014.

Abstract

Norepinephrine regulates latent neural stem cell activity and adult hippocampal neurogenesis, and has an important role in modulating hippocampal functions such as learning, memory and mood. Adult hippocampal neurogenesis is a multi-stage process, spanning from the activation and proliferation of hippocampal stem cells, to their differentiation into neurons. However, the stage-specific effects of noradrenergic receptors in regulating adult hippocampal neurogenesis remain poorly understood. In this study, we used transgenic Nestin-GFP mice and neurosphere assays to show that modulation of α2- and β-adrenergic receptor activity directly affects Nestin-GFP/GFAP-positive precursor cell population albeit in an opposing fashion. While selective stimulation of α2-adrenergic receptors decreases precursor cell activation, proliferation and immature neuron number, stimulation of β-adrenergic receptors activates the quiescent precursor pool and enhances their proliferation in the adult hippocampus. Furthermore, our data indicate no major role for α1-adrenergic receptors, as we did not observe any change in either the activation and proliferation of hippocampal precursors following selective stimulation or blockade of α1-adrenergic receptors. Taken together, our data suggest that under physiological as well as under conditions that lead to enhanced norepinephrine release, the balance between α2- and β-adrenergic receptor activity regulates precursor cell activity and hippocampal neurogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-2 Receptor Agonists / pharmacology*
  • Adrenergic alpha-2 Receptor Antagonists / pharmacology
  • Adrenergic beta-Agonists / pharmacology*
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Hippocampus / growth & development
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nestin / genetics
  • Nestin / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / drug effects*
  • Neural Stem Cells / metabolism
  • Neurogenesis*

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • Adrenergic alpha-2 Receptor Antagonists
  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Nestin

Grants and funding

This work was supported by an Indo-Queensland Biotechnology Project Fund Award from the Queensland Government and the Estate of Dr. Clem Jones AO to PFB and the Department of Biotechnology, Government of India to VAV and by TIFR intramural funds (VAV). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.