β-amyloid-induced apoptosis of cerebellar granule cells and cortical neurons:: exacerbation by selective inhibition of group I metabotropic glutamate receptors

Administration of beta-amyloid fragment 25-35 (A beta(25-35)) to cultured rat cerebellar granule cells (CGC) or cortical neurons caused cell death that was characterized by morphological and nuclear changes consistent with apoptosis. Inhibition of NMDA receptors produced a mild exacerbation of A beta(25-35) toxicity in cortical neurons; a similar effect was induced by AMPA/kainate receptor inhibition in CGC. Selective activation of group I metabotropic glutamate receptors (mGluR) by dihyroxyphenylglycine (DHPG) had no effect on A beta(25-25)-induced apoptosis in either cell type, and was unaffected by blockade of ionotropic glutamate receptors. In contrast selective inhibition of group I mGluR by (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) exacerbated A beta toxicity in cortical neurons, whereas this treatment was without effect on CGC. However, AIDA significantly increased A beta-induced apoptosis in CGC in the presence of either NMDA or AMPA/kainate receptor inhibition; blockade of both ionotropic glutamate receptor classes further increased the exacerbation of apoptosis following treatment with AIDA. These findings suggest that A beta(25-35)-induced neuronal injury leads to activation of group I mGluR, which attenuates the resulting apoptosis. (C) 1999 Elsevier Science Ltd. All rights reserved.