New evidences for a role of mGluR7 in astrocyte survival: Possible implications for neuroprotection

Neuropharmacology
D JantasW Lason

Abstract

A specific activation of metabotropic glutamate receptor 7 (mGluR7) has been shown to be neuroprotective in various models of neuronal cell damage, however, its role in glia cell survival has not been studied, yet. Thus, we performed comparative experiments estimating protective effects of the mGluR7 allosteric agonist AMN082 in glia, neuronal and neuronal-glia cell cultures against various harmful stimuli. First, the transcript levels of mGluR7 and other subtypes of group II and III mGluRs in cortical neuronal, neuronal-glia and glia cell cultures have been measured by qPCR method. Next, we demonstrated that AMN082 with similar efficiency attenuated the glia cell damage evoked by staurosporine (St) and doxorubicin (Dox). The AMN082-mediated glioprotection was mGluR7-dependent and associated with decreased DNA fragmentation without involvement of caspase-3 inhibition. Moreover, the inhibitors of PI3K/Akt and MAPK/ERK1/2 pathways blocked the protective effect of AMN082. In neuronal and neuronal-glia cell cultures in the model of glutamate (Glu)- but not St-evoked cell damage, we showed a significant glia contribution to mGluR7-mediated neuroprotection. Finally, by using glia and neuronal cells derived from mGluR7+/+ and mGluR7-/...Continue Reading

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