Norepinephrine directly activates adult hippocampal precursors via beta(3)-adrenergic receptors

Jhaveri, Dhanisha J., Mackay, Eirinn W., Hamlin, Adam S., Marathe, Swananda V., Nandam, L. Sanjay, Vaidya, Vidita A. and Bartlett, Perry F. (2010) Norepinephrine directly activates adult hippocampal precursors via beta(3)-adrenergic receptors. Journal of Neuroscience, 30 7: 2795-2806. doi:10.1523/JNEUROSCI.3780-09.2010

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Author Jhaveri, Dhanisha J.
Mackay, Eirinn W.
Hamlin, Adam S.
Marathe, Swananda V.
Nandam, L. Sanjay
Vaidya, Vidita A.
Bartlett, Perry F.
Title Norepinephrine directly activates adult hippocampal precursors via beta(3)-adrenergic receptors
Formatted title
Norepinephrine directly activates adult hippocampal precursors via β3-adrenergic receptors
Journal name Journal of Neuroscience   Check publisher's open access policy
ISSN 0270-6474
Publication date 2010-02-17
Sub-type Article (original research)
DOI 10.1523/JNEUROSCI.3780-09.2010
Open Access Status File (Publisher version)
Volume 30
Issue 7
Start page 2795
End page 2806
Total pages 12
Editor John H. R. Maunsell
Place of publication Washington DC, United States
Publisher Society for Neuroscience
Collection year 2011
Language eng
Subject 1109 Neurosciences
1702 Cognitive Sciences
Formatted abstract
Adult hippocampal neurogenesis is a critical form of cellular plasticity that is greatly influenced by neural activity. Among the neurotransmitters that are widely implicated in regulating this process are serotonin and norepinephrine, levels of which are modulated by stress, depression and clinical antidepressants. However, studies to date have failed to address a direct role for either neurotransmitter in regulating hippocampal precursor activity. Here we show that norepinephrine but not serotonin directly activates self-renewing and multipotent neural precursors, including stem cells, from the hippocampus of adult mice. Mechanistically, we provide evidence that β3-adrenergic receptors, which are preferentially expressed on a Hes5-expressing precursor population in the subgranular zone (SGZ), mediate this norepinephrine-dependent activation. Moreover, intrahippocampal injection of a selective β3-adrenergic receptor agonist in vivo increases the number of proliferating cells in the SGZ. Similarly, systemic injection of the β-adrenergic receptor agonist isoproterenol not only results in enhancement of proliferation in the SGZ but also leads to an increase in the percentage of nestin/glial fibrillary acidic protein double-positive neural precursors in vivo. Finally, using a novel ex vivo “slice-sphere” assay that maintains an intact neurogenic niche, we demonstrate that antidepressants that selectively block the reuptake of norepinephrine, but not serotonin, robustly increase hippocampal precursor activity via β-adrenergic receptors. These findings suggest that the activation of neurogenic precursors and stem cells via β3-adrenergic receptors could be a potent mechanism to increase neuronal production, providing a putative target for the development of novel antidepressants.
Copyright © 2010 the authors
Keyword Chronic antidepressant treatment
Serotonin reuptake inhibitors
Neural stem-cells
Dentate gyrus
Chronic fluoxetine
Agonist SR58611A
Progenitor cells
Rat hippocampus
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published under "Development/Plasticity/Repair"

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 63 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 65 times in Scopus Article | Citations
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Created: Sun, 07 Mar 2010, 00:03:01 EST