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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.

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.
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.
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
VIP, stem cells, neurogenesis, cell fate, cell death, symmetric cell division
1066-5099
2539-2551
Zaben, Malik
6390c24c-4458-486d-9188-3afda5c91359
Sheward, W. John
56338cd5-265e-44fc-a160-dfb24a95d26a
Shtaya, Anan
15b0b2b2-20db-49bf-aa7f-af49d6e3360f
Abbosh, Christopher
fa7d12fb-1e6e-4924-ad08-4be6b422278e
Harmar, Anthony J.
4cb22115-0a9d-47ec-ad63-ebb1b92cf374
Pringle, Ashley K.
6339ed95-c491-43a8-b2fb-2384466dc80d
Gray, William P.
f34a0e23-3cba-4b0a-8676-a1b2c3e4c095
Zaben, Malik
6390c24c-4458-486d-9188-3afda5c91359
Sheward, W. John
56338cd5-265e-44fc-a160-dfb24a95d26a
Shtaya, Anan
15b0b2b2-20db-49bf-aa7f-af49d6e3360f
Abbosh, Christopher
fa7d12fb-1e6e-4924-ad08-4be6b422278e
Harmar, Anthony J.
4cb22115-0a9d-47ec-ad63-ebb1b92cf374
Pringle, Ashley K.
6339ed95-c491-43a8-b2fb-2384466dc80d
Gray, William P.
f34a0e23-3cba-4b0a-8676-a1b2c3e4c095

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), 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

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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: 1066-5099
PURE UUID: f847e9d5-bf6c-47be-a2c2-3dd764c0c061
ORCID for Ashley K. Pringle: ORCID iD orcid.org/0000-0003-2421-4380

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Date deposited: 05 Mar 2010
Last modified: 14 Mar 2024 02:38

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Contributors

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

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