Activation of Group III Metabotropic Glutamate Receptor Reduces Intracellular Calcium in β-Amyloid Peptide [31–35]-Treated Cortical Neurons

Abstract

It is unknown whether amyloid beta-protein 31–35 (Aβ[31–35]) has effects similar to Aβ[1–40] and Aβ[25–35] on the intracellular calcium ([Ca²⁺]i) to induce a disruption of calcium homeostasis. In this study, we investigated the effects of Aβ[31–35] on [Ca²⁺]i in primary cultured cortical neurons using real time fluorescence imaging technique and the Ca²⁺-sensitive dye Furo-2/AM. It was found that Aβ[31–35] (25 μM) could induce a significant elevation in [Ca²⁺]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 [Ca²⁺]i and protect neurons from apoptosis induced by Aβ[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 [Ca²⁺]i and apoptosis in neurons treated by Aβ[31–35]. We demonstrated that l-SOP or (R,S)-PPG (100 μM) treatment suppresses significantly the elevation of [Ca²⁺]i induced by Aβ[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 Aβ[31–35] may be the shortest sequence responsible for the neuronal toxicity of Aβ protein and that the neuroprotective role of the activation of group III mGluRs from the apoptosis induced by Aβ[31–35] might be partly due to its ability to inhibit the increased calcium influx, which results from Aβ[31–35].