Enhancement of glutamate uptake mediates the neuroprotection exerted by activating group II or III metabotropic glutamate receptors on astrocytes
Article first published online: 26 JAN 2005
Journal of Neurochemistry
Volume 92, Issue 4, pages 948–961, February 2005
How to Cite
Yao, H.-H., Ding, J.-H., Zhou, F., Wang, F., Hu, L.-F., Sun, T. and Hu, G. (2005), Enhancement of glutamate uptake mediates the neuroprotection exerted by activating group II or III metabotropic glutamate receptors on astrocytes. Journal of Neurochemistry, 92: 948–961. doi: 10.1111/j.1471-4159.2004.02937.x
- Issue published online: 26 JAN 2005
- Article first published online: 26 JAN 2005
- Received May 20, 2004; revised manuscript received September 17, 2004; accepted October 25, 2004.
- C6 glioma cells;
- glutamate uptake;
- metabotropic glutamate receptors;
- Parkinson's disease
We investigated whether the activation of astroglial group II and III metabotropic glutamate receptors (mGluRs) could exert neuroprotective effects and whether the neuroprotection was related to glutamate uptake. Our results showed that the activation of astroglial group II or III mGluRs exerted neuroprotection against 1-methyl-4-phenylpyridinium (MPP+) astroglial conditioned medium-induced neurotoxicity in midbrain neuron cultures. Furthermore, MPP+ decreased glutamate uptake of primary astrocytes and C6 glioma cells, which was recovered by activating group II or III mGluRs. Specific group II or III mGluRs antagonists completely abolished the neuroprotective effects and the enhancement of glutamate uptake of their respective agonists. Our results showed that the primary cultured rat astrocytes and C6 glioma cells expressed receptor proteins for group II mGluR2/3, group III mGluR4, mGluR6 and mGluR7. C6 glioma cells expressed mRNA for group II mGluR3, group III mGluR4, mGluR6, mGluR7 and mGluR8. In conclusion, we confirmed that the activation of astroglial mGluRs exerted neuroprotection, and demonstrated that the mechanism underlying this protective role was at least partially related to the enhancement of glutamate uptake.