Retracted: Neuroprotection mediated by glial group-II metabotropic glutamate receptors requires the activation of the MAP kinase and the phosphatidylinositol-3-kinase pathways
Article first published online: 20 DEC 2001
Journal of Neurochemistry
Volume 78, Issue 3, pages 435–445, August 2001
How to Cite
D'Onofrio, M., Cuomo, L., Battaglia, G., Ngomba, R. T., Storto, M., Kingston, A. E., Orzi, F., De Blasi, A., Di Iorio, P., Nicoletti, F. and Bruno, V. (2001), Retracted: Neuroprotection mediated by glial group-II metabotropic glutamate receptors requires the activation of the MAP kinase and the phosphatidylinositol-3-kinase pathways. Journal of Neurochemistry, 78: 435–445. doi: 10.1046/j.1471-4159.2001.00435.x
- Issue published online: 20 DEC 2001
- Article first published online: 20 DEC 2001
- Received October 31, 2000; revised manuscript received February 27, 2001; accepted February 27, 2001.
Vol. 129, Issue 6, 1035, Article first published online: 28 APR 2014
- MAP kinase;
- mGlu receptors;
The mGlu2/3 receptor agonists 4-carboxy-3-hydroxyphenylglycine (4C3HPG) and LY379268 attenuated NMDA toxicity in primary cultures containing both neurons and astrocytes. Neuroprotection was abrogated by PD98059 and LY294002, which inhibit the mitogen activated protein kinase (MAPK) and the phosphatidylinositol-3-kinase (PI-3-K) pathways, respectively. Cultured astrocytes lost the ability to produce transforming growth factor-β1 (TGF-β1) in response to mGlu2/3 receptor agonists when co-incubated with PD98059 or LY294002. As a result, the glial medium was no longer protective against NMDA toxicity. Activation of the MAPK and PI-3-K pathways in cultured astrocytes treated with 4C3HPG or LY379268 was directly demonstrated by an increase in the phosphorylated forms of ERK-1/2 and Akt. Similarly to that observed in the culture, intracerebral or systemic injections of mGlu2/3 receptor agonists enhanced TGF-β1 formation in the rat or mouse caudate nucleus, and this effect was reduced by PD98059. PD98059 also reduced the ability of LY379268 to protect striatal neurons against NMDA toxicity. These results suggest that activation of glial mGlu2/3 receptors induces neuroprotection through the activation of the MAPK and PI-3-K pathways leading to the induction of TGF-β.