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Group III metabotropic glutamate receptor activation suppresses self-replication of undifferentiated neocortical progenitor cells.
- Source :
-
Journal of neurochemistry [J Neurochem] 2008 Jun; Vol. 105 (5), pp. 1996-2012. Date of Electronic Publication: 2008 Feb 07. - Publication Year :
- 2008
-
Abstract
- We evaluated the possible functional expression of metabotropic glutamate receptors (mGluRs) by neural progenitors from embryonic mouse neocortex. Constitutive expression was seen with group I, II, and III mGluRs in undifferentiated cells and neurospheres formed by clustered cells during culture with epidermal growth factor. The group III mGluR agonist, L-2-amino-4-phosphonobutyrate, drastically reduced proliferation activity at 1-100 microM without inducing cell death, with group I and group II mGluR agonists being ineffective, in these neurospheres. Both forskolin and a group III mGluR antagonist significantly increased the proliferation alone, but significantly prevented the suppression by L-2-amino-4-phosphonobutyrate. Activation of group III mGluR significantly decreased mRNA expression of the cell cycle regulator cyclinD1, in addition to inhibiting the transactivation mediated by cAMP of cyclinD1 gene in the pluripotent P19 progenitor cells. Prior activation of group III mGluR led to a significant decrease in the number of cells immunoreactive for a neuronal marker, with an increase in that for an astroglial marker irrespective of differentiation inducers. These results suggest that group III mGluR may be functionally expressed to suppress self-renewal capacity through a mechanism related to cAMP formation with promotion of subsequent differentiation into astroglial lineage in neural progenitors.
- Subjects :
- Animals
Cell Line, Tumor
Cells, Cultured
Growth Inhibitors physiology
Mice
Neocortex cytology
Receptors, Metabotropic Glutamate physiology
Stem Cells cytology
Cell Differentiation physiology
Growth Inhibitors metabolism
Neocortex metabolism
Receptors, Metabotropic Glutamate metabolism
Stem Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1471-4159
- Volume :
- 105
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 18266930
- Full Text :
- https://doi.org/10.1111/j.1471-4159.2008.05289.x