EN
A number of studies have shown neuroprotective effects of agonists of group-II metabotropic glutamate receptors (mGluR II) in various experimental models of excitotoxicity. However, an influence of these compounds on neuronal apoptosis is less recognized. We tested the effect of nonspecific agonist of mGluR II, LY354740 ((+)-2-aminobicyclo[3.1.0]hexane-2,6dicarboxylate) on staurosporine and doxorubicin evoked cell death in primary pure neuronal and neuronal-glial cortical cells, as well in cerebellar granule cells (CGC). We found that LY354740 (0.01-10 microM) was protective against staurosporine-evoked cell death in both, pure cortical neurons and CGC with higher efficacy in 12 DIV in comparison with the 7 DIV ones. Moreover, the neuroprotective effect of LY354470 in neuronal-glial cells did not differ from that found in pure neurons. The protective effect of mGluR II agonist was not connected with attenuation the St-induced caspase-3 activity and DNA fragmentation, but this agent decreased the St-evoked necrotic cell death as measured by propidium ioide staining. LY354470 had no influence on doxorubicin-evoked cell death, but attenuated the glutamate-mediated neuronal cell damage. Our data suggest that neuroprotective effects of the mGluR II ligand are stimuli- and development-dependent and are rather connected with attenuation of necrotic-, than the apoptotic cell death. The study was supported by grant No NN405611638 from the Ministry of Science and Higher Education, Warsaw, Poland.