Group I Metabotropic Glutamate Receptors

A Potential Target for Regulation of Proliferation and Differentiation of an Immortalized Human Neural Stem Cell Line

Julie Ladeby Erichsen, Morten Blaabjerg, Helle Bogetofte Thomasen, Alberto Martinez Serrano, Morten Meyer

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Human neural stem cells (NSCs) from the developing embryo or the subventricular zone of the adult brain can potentially elicit brain repair after injury or disease, either via endogenous cell proliferation or by cell transplantation. Profound knowledge of the diverse signals affecting these cells is, however, needed to realise their therapeutic potential. Glutamate and group I metabotropic glutamate receptors (mGluRs) affect proliferation and survival of rodent NSCs both during embryonic and postnatal development. To investigate the role of group I mGluRs (mGluR1 and mGluR5) on human NSCs, we differentiated an immortalized, forebrain-derived stem cell line in the presence or absence of glutamate and with addition of either the group I mGluR agonist DHPG or the selective antagonists; MPEP (mGluR5) and LY367385 (mGluR1). Characterization of differentiated cells revealed that both mGluR1 and mGluR5 were present on the cells. Addition of glutamate to the growth medium significantly increased cell proliferation and reduced cell death, resulting in increased cell numbers. In the presence of glutamate, selective activation of group I mGluRs reduced gliogenesis, whereas selective inhibition of group I mGluRs reduced neurogenesis. Our results substantiate the importance of glutamate signalling in regulation of human NSCs and may as such be applied to promote proliferation and neuronal differentiation. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalBasic & Clinical Pharmacology & Toxicology
Volume116
Issue number4
Pages (from-to)329-336
ISSN1742-7835
DOIs
Publication statusPublished - 2015

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Metabotropic Glutamate Receptors
Stem cells
Glutamic Acid
Cell Line
Cell proliferation
alpha-methyl-4-carboxyphenylglycine
Brain
Cell Proliferation
Lateral Ventricles
Cell death
Rodentia
Repair
Cell Death
Embryonic Structures
Chemical activation
Wounds and Injuries
Growth
metabotropic glutamate receptor type 1

Cite this

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title = "Group I Metabotropic Glutamate Receptors: A Potential Target for Regulation of Proliferation and Differentiation of an Immortalized Human Neural Stem Cell Line",
abstract = "Human neural stem cells (NSCs) from the developing embryo or the subventricular zone of the adult brain can potentially elicit brain repair after injury or disease, either via endogenous cell proliferation or by cell transplantation. Profound knowledge of the diverse signals affecting these cells is, however, needed to realise their therapeutic potential. Glutamate and group I metabotropic glutamate receptors (mGluRs) affect proliferation and survival of rodent NSCs both during embryonic and postnatal development. To investigate the role of group I mGluRs (mGluR1 and mGluR5) on human NSCs, we differentiated an immortalized, forebrain-derived stem cell line in the presence or absence of glutamate and with addition of either the group I mGluR agonist DHPG or the selective antagonists; MPEP (mGluR5) and LY367385 (mGluR1). Characterization of differentiated cells revealed that both mGluR1 and mGluR5 were present on the cells. Addition of glutamate to the growth medium significantly increased cell proliferation and reduced cell death, resulting in increased cell numbers. In the presence of glutamate, selective activation of group I mGluRs reduced gliogenesis, whereas selective inhibition of group I mGluRs reduced neurogenesis. Our results substantiate the importance of glutamate signalling in regulation of human NSCs and may as such be applied to promote proliferation and neuronal differentiation. This article is protected by copyright. All rights reserved.",
author = "Erichsen, {Julie Ladeby} and Morten Blaabjerg and {Bogetofte Thomasen}, Helle and Serrano, {Alberto Martinez} and Morten Meyer",
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Group I Metabotropic Glutamate Receptors : A Potential Target for Regulation of Proliferation and Differentiation of an Immortalized Human Neural Stem Cell Line. / Erichsen, Julie Ladeby; Blaabjerg, Morten; Bogetofte Thomasen, Helle; Serrano, Alberto Martinez; Meyer, Morten.

In: Basic & Clinical Pharmacology & Toxicology, Vol. 116, No. 4, 2015, p. 329-336.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Group I Metabotropic Glutamate Receptors

T2 - A Potential Target for Regulation of Proliferation and Differentiation of an Immortalized Human Neural Stem Cell Line

AU - Erichsen, Julie Ladeby

AU - Blaabjerg, Morten

AU - Bogetofte Thomasen, Helle

AU - Serrano, Alberto Martinez

AU - Meyer, Morten

N1 - This article is protected by copyright. All rights reserved.

PY - 2015

Y1 - 2015

N2 - Human neural stem cells (NSCs) from the developing embryo or the subventricular zone of the adult brain can potentially elicit brain repair after injury or disease, either via endogenous cell proliferation or by cell transplantation. Profound knowledge of the diverse signals affecting these cells is, however, needed to realise their therapeutic potential. Glutamate and group I metabotropic glutamate receptors (mGluRs) affect proliferation and survival of rodent NSCs both during embryonic and postnatal development. To investigate the role of group I mGluRs (mGluR1 and mGluR5) on human NSCs, we differentiated an immortalized, forebrain-derived stem cell line in the presence or absence of glutamate and with addition of either the group I mGluR agonist DHPG or the selective antagonists; MPEP (mGluR5) and LY367385 (mGluR1). Characterization of differentiated cells revealed that both mGluR1 and mGluR5 were present on the cells. Addition of glutamate to the growth medium significantly increased cell proliferation and reduced cell death, resulting in increased cell numbers. In the presence of glutamate, selective activation of group I mGluRs reduced gliogenesis, whereas selective inhibition of group I mGluRs reduced neurogenesis. Our results substantiate the importance of glutamate signalling in regulation of human NSCs and may as such be applied to promote proliferation and neuronal differentiation. This article is protected by copyright. All rights reserved.

AB - Human neural stem cells (NSCs) from the developing embryo or the subventricular zone of the adult brain can potentially elicit brain repair after injury or disease, either via endogenous cell proliferation or by cell transplantation. Profound knowledge of the diverse signals affecting these cells is, however, needed to realise their therapeutic potential. Glutamate and group I metabotropic glutamate receptors (mGluRs) affect proliferation and survival of rodent NSCs both during embryonic and postnatal development. To investigate the role of group I mGluRs (mGluR1 and mGluR5) on human NSCs, we differentiated an immortalized, forebrain-derived stem cell line in the presence or absence of glutamate and with addition of either the group I mGluR agonist DHPG or the selective antagonists; MPEP (mGluR5) and LY367385 (mGluR1). Characterization of differentiated cells revealed that both mGluR1 and mGluR5 were present on the cells. Addition of glutamate to the growth medium significantly increased cell proliferation and reduced cell death, resulting in increased cell numbers. In the presence of glutamate, selective activation of group I mGluRs reduced gliogenesis, whereas selective inhibition of group I mGluRs reduced neurogenesis. Our results substantiate the importance of glutamate signalling in regulation of human NSCs and may as such be applied to promote proliferation and neuronal differentiation. This article is protected by copyright. All rights reserved.

U2 - 10.1111/bcpt.12324

DO - 10.1111/bcpt.12324

M3 - Journal article

VL - 116

SP - 329

EP - 336

JO - Basic & Clinical Pharmacology & Toxicology

JF - Basic & Clinical Pharmacology & Toxicology

SN - 1742-7835

IS - 4

ER -