Activation of group I metabotropic glutamate receptors reduces neuronal apoptosis but increases necrotic cell death in vitro

Glutamate released during acute CNS insults acts at metabotropic glutamate receptors (mGluR), including group I mGluR, Blockade of group I mGluR durin g in vitro neuronal trauma provides neuroprotection, whereas activation exa cerbates such injury. However, the effects of group I mGluR agonists or ant agonists have been primarily studied in in vitro models characterized by ne crotic cell death. We examined the role of group I mGluR in the modulation of neuronal injury induced during oxygen-glucose deprivation (OGD), a well- studied model of necrosis, and by application of two well established pro-a poptotic agents: staurosporine and etoposide. Inhibition of group I mGluR a ttenuated necrosis induced by OGD, whereas selective activation of group 1 mGluR exacerbated such injury. In contrast, activation of group I mGluR, in cluding selective activation of mGluR5, significantly attenuated apoptotic cell death induced by both staurosporine and etoposide, This effect was com pletely reversed by coapplication of a group I mGluR antagonist. Thus, grou p I mGluR appear to exhibit opposite effects on necrotic and apoptotic neur onal cell death. Our findings suggest that activation of mGluR1 exacerbates neuronal necrosis whereas both mGluR1 and mGluR5 play a role in attenuatio n of neuronal apoptosis.