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 realize their therapeutic potential. Glutamate and group I metabotropic glutamate receptors (mGluRs) affect proliferation and survival of rodent NSCs both during embryonic and post-natal 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 the regulation of human NSCs and may as such be applied to promote proliferation and neuronal differentiation.
authors.affiliation: Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Julie Ladeby
authors.initials: JL
authors.lastname: Erichsen
authors.forename: Morten
authors.initials: M
authors.lastname: Blaabjerg
authors.forename: Helle
authors.initials: H
authors.lastname: Bogetofte
authors.forename: Alberto Martinez
authors.initials: AM
authors.lastname: Serrano
authors.forename: Morten
authors.initials: M
authors.lastname: Meyer
mesh_terms: D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects; D016548:Prosencephalon / Q000166:cytology; D064529:Receptor, Metabotropic Glutamate 5 / Q000187:drug effects; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects*
chemical_list: C578935:GRM5 protein, human; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D007770:L-Lactate Dehydrogenase