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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
Author(s) -
Erichsen Julie Ladeby,
Blaabjerg Morten,
Bogetofte Helle,
Serrano Alberto Martinez,
Meyer Morten
Publication year - 2015
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12324
Subject(s) - metabotropic glutamate receptor , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 5 , subventricular zone , neural stem cell , glutamate receptor , metabotropic glutamate receptor 7 , metabotropic glutamate receptor 6 , neurogenesis , biology , neuroscience , microbiology and biotechnology , metabotropic glutamate receptor 4 , stem cell , receptor , biochemistry
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 ( mG luRs) affect proliferation and survival of rodent NSCs both during embryonic and post‐natal development. To investigate the role of group I mG luRs ( mG luR1 and mG luR5) 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 mG luR agonist DHPG or the selective antagonists, MPEP ( mG luR5) and LY367385 ( mG luR1). Characterization of differentiated cells revealed that both mG luR1 and mG luR5 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 mG luRs reduced gliogenesis, whereas selective inhibition of group I mG luRs 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.