β-amyloid-induced apoptosis of cerebellar granule cells and cortical neurons:: exacerbation by selective inhibition of group I metabotropic glutamate receptors
β-amyloid-induced apoptosis of cerebellar granule cells and cortical neurons:: exacerbation by selective inhibition of group I metabotropic glutamate receptors
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DOI：
10.1016/s0028-3908(99)00044-1
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发表时间：
1999-08-01
影响因子：
4.7
通讯作者：
Faden, AI
中科院分区：
文献类型：
--
作者：
Allen, JW;Eldadah, BA;Faden, AI
给培养的大鼠小脑颗粒细胞(CGC)或皮质神经元注射β-淀粉样蛋白片段25-35(Aβ(25-35))可引起细胞死亡，其特征是形态和核的变化与细胞凋亡一致。抑制NMDA受体可轻度加重Aβ(25-35)对皮层神经元的毒性作用；抑制AMPA/海人藻酸受体对CGC的毒性作用与此类似。二羟基苯甘氨酸(DHPG)选择性激活I型代谢型谷氨酸受体(MGluR)对Aβ(25-25)诱导的细胞凋亡无影响，也不受离子型谷氨酸受体阻断的影响。相反，(RS)-1-氨基-1，5-二羧酸(AIDA)选择性抑制I组mGluR可加重皮质神经元的Aβ毒性，而对CGC无影响。然而，在NMDA或AMPA/海人藻酸受体被抑制的情况下，AIDA显著增加了Aβ诱导的CGC细胞的凋亡；阻断这两种离子亲性谷氨酸受体进一步加剧了AIDA处理后的细胞凋亡。这些结果表明，Aβ(25-35)诱导的神经元损伤导致I组mGluR的激活，从而减弱由此产生的细胞凋亡。(C)1999爱思唯尔科学有限公司。保留所有权利。
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.