The University of Southampton
University of Southampton Institutional Repository

The neurotransmitter VIP expands the pool of symmetrically dividing postnatal dentate gyrus precursors via VPAC(2) receptors, or directs them towards a neuronal fate via VPAC(1) receptors.

Zaben, Malik, Sheward, W. John, Shtaya, Anan, Abbosh, Christopher, Harmar, Anthony J., Pringle, Ashley K. and Gray, William P. (2009) The neurotransmitter VIP expands the pool of symmetrically dividing postnatal dentate gyrus precursors via VPAC(2) receptors, or directs them towards a neuronal fate via VPAC(1) receptors. Stem Cells, 27, (10), pp. 2539-2551. (doi:10.1002/stem.184).

Record type: Article

Abstract

The controlled production of neurons in the postnatal dentate gyrus and thoughout life is important for hippocampal learning and memory. The mechanisms underlying the necessary coupling of neuronal activity to neural stem/progenitor cell (NSPC) function remain poorly understood. Within the dentate subgranular stem cell niche, local interneurons appear to play an important part in this excitation-neurogenesis coupling via GABAergic transmission, which promotes neuronal differentiation and integration. Here we show that vasoactive intestinal polypeptide, a neuropeptide coreleased with GABA under specific firing conditions, is uniquely trophic for proliferating postnatal nestin-positive dentate NSPCs, mediated via the VPAC2 receptor. We also show that VPAC2 receptor activation shifts the fate of symmetrically dividing NSPCs toward a nestin-only phenotype, independent of the trophic effect. In contrast, selective VPAC1 receptor activation shifts NSPC fate toward granule cell neurogenesis without any trophism. We confirm a trophic role for VPAC2 receptors in vivo, showing reduced progeny survival and dentate neurogenesis in adult Vipr2-/- mice. We also show a specific reduction in type 2 nestin-positive precursors in vivo, consistent with a role for VPAC2 in maintaining this cell population. This work provides the first evidence of differential fate modulation of neurogenesis by neurotransmitter receptor subtypes and extends the fate-determining effects of neurotransmitters to maintaining the nestin-positive pool of NSPCs. This differential receptor effect may support the independent pharmacological manipulation of precursor pool expansion and neurogenic instruction for therapeutic application in the treatment of cognitive deficits associated with a decline in neurogenesis

Full text not available from this repository.

More information

Published date: October 2009
Keywords: VIP, stem cells, neurogenesis, cell fate, cell death, symmetric cell division

Identifiers

Local EPrints ID: 73343
URI: http://eprints.soton.ac.uk/id/eprint/73343
ISSN: 0250-6793
PURE UUID: f847e9d5-bf6c-47be-a2c2-3dd764c0c061
ORCID for Ashley K. Pringle: ORCID iD orcid.org/0000-0003-2421-4380

Catalogue record

Date deposited: 05 Mar 2010
Last modified: 18 Jul 2017 23:50

Export record

Altmetrics

Contributors

Author: Malik Zaben
Author: W. John Sheward
Author: Anan Shtaya
Author: Christopher Abbosh
Author: Anthony J. Harmar
Author: William P. Gray

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×