Abstract
The use of neural progenitor cells (NPCs) is limited by the incomplete knowledge of the extracellular signals regulating their proliferation and survival. We report that cultured mouse NPCs express functional mGlu3 and mGlu5 metabotropic glutamate receptors. Pharmacological blockade of both receptors reduced NPC proliferation and survival, whereas activation of mGlu5 receptors substantially enhanced cell proliferation. Adult mice lacking mGlu5 receptors or treated with mGlu5 or mGlu3 receptor antagonists showed a dramatic reduction in the number of dividing neuroprogenitors present in the subventricular zone and in the dentate gyrus of the hippocampus. These data disclose a novel function of mGlu receptors and offer new potential strategies for the optimization of cell replacement therapy in neurodegenerative disorders.
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Abbreviations
- NPC:
-
neuroprogenitor cells
- mGlu:
-
metabotropic glutamate receptors
- CNS:
-
central nervous system
- EGF:
-
epidermal growth factor
- bFGF:
-
basic Fibroblast Growth Factor
- GFAP:
-
glial fibrillar acidic protein
- Tuj1:
-
beta III tubulin (clone J1)
- GalC:
-
galactocerebroside
- NBQX:
-
1,2,3,4-tetrahydro6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide
- PI:
-
polyphosphoinositide
- MPEP:
-
2-methyl-6-(phenylethynyl) pyridine
- MAPK:
-
mitogen-activated protein kinase
- DHPG:
-
3,5-dihydroxyphenylglycine
- PI-3-K:
-
phosphatidylinositol-3-kinase
- BrdU:
-
bromodeoxyuridine
- DG:
-
dentate gyrus
- SVZ:
-
subventricular zone
- cAMP:
-
cyclic AMP
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Acknowledgements
This work is dedicated to the memory of Dr. Stefano Pagano and was supported by the Telethon Grant 1238.
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Di Giorgi-Gerevini, V., Melchiorri, D., Battaglia, G. et al. Endogenous activation of metabotropic glutamate receptors supports the proliferation and survival of neural progenitor cells. Cell Death Differ 12, 1124–1133 (2005). https://doi.org/10.1038/sj.cdd.4401639
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DOI: https://doi.org/10.1038/sj.cdd.4401639
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