Activation of group III metabotropic glutamate receptor reduces intracellular calcium in beta-amyloid peptide [31-35]-treated cortical neurons.

It is unknown whether amyloid beta-protein 31-35 (Abeta[31-35]) has effects similar to Abeta[1-40] and Abeta[25-35] on the intracellular calcium ([Ca(2+)]i) to induce a disruption of calcium homeostasis. In this study, we investigated the effects of Abeta[31-35] on [Ca(2+)]i in primary cultured cortical neurons using real time fluorescence imaging technique and the Ca(2+)-sensitive dye Furo-2/AM. It was found that Abeta[31-35] (25 microM) could induce a significant elevation in [Ca(2+)]i and a decrease in the average latency in the cortical neurons in a dose-dependent manner. To examine whether the activation of group III mGluRs could block the changes in [Ca(2+)]i and protect neurons from apoptosis induced by Abeta[31-35], we then investigated the effects of L: -serine-O-phosphate (L: -SOP) and (R,S)-4-phosphonophenylglycine ((R,S)-PPG), the selective agonists of group III metabotropic glutamate receptors (mGluRs), on [Ca(2+)]i and apoptosis in neurons treated by Abeta[31-35]. We demonstrated that L: -SOP or (R,S)-PPG (100 microM) treatment suppresses significantly the elevation of [Ca(2+)]i induced by Abeta[31-35] and also induces an almost complete recovery of both the fluorescence intensity and apoptotic cells (%) to the control level in the neurons. These results suggest that Abeta[31-35] may be the shortest sequence responsible for the neuronal toxicity of Abeta protein and that the neuroprotective role of the activation of group III mGluRs from the apoptosis induced by Abeta[31-35] might be partly due to its ability to inhibit the increased calcium influx, which results from Abeta[31-35].