Bruno V, Sureda F X, Storto M, Casabona G, Caruso A, Knopfel T, Kuhn R, Nicoletti F
I. N. M. Neuromed, Pozzilli, Italy.
J Neurosci. 1997 Mar 15;17(6):1891-7. doi: 10.1523/JNEUROSCI.17-06-01891.1997.
The group-II metabotropic glutamate (mGlu) receptor agonists (2S,1'R, 2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV), S-4-carboxy-3-hydroxyphenylglycine (4C3HPG), and (2S,1'S, 2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I) protected mouse cortical neurons grown in mixed cultures against excitotoxic degeneration induced by a 10 min pulse with NMDA. Protection was observed not only when agonists were added in combination with NMDA but also when they were transiently applied to cultures 6-20 hr before the NMDA pulse. In both cases, neuroprotection was reduced by the group-II mGlu receptor antagonist (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine (PCCG-IV), as well as by the protein synthesis inhibitor cycloheximide (CHX). Both neurons and astrocytes in mixed cultures were immunostained with an antibody that recognized mGlu2 and mGlu3 receptors in recombinant cells. To determine whether astrocytes played any role in the neuroprotection mediated by group-II mGlu receptors, we exposed pure cultures of cortical astrocytes to DCG-IV, 4C3HPG, or L-CCG-I for 10 min. The astrocyte medium collected 2-20 hr after the exposure to any of these drugs was highly neuroprotective when transferred to mixed cultures treated with NMDA. This protective activity was reduced when CHX was applied to astrocyte cultures immediately after the transient exposure to group-II mGlu receptor agonists. We conclude that neuroprotection mediated by group-II mGlu receptors in cultured cortical cells requires new protein synthesis and involves an interaction between neurons and astrocytes.
II 型代谢型谷氨酸（mGlu）受体激动剂（2S,1'R,2'R,3'R）-2-（2,3-二羧基环丙基）甘氨酸（DCG-IV）、S-4-羧基-3-羟基苯甘氨酸（4C3HPG）和（2S,1'S,2'S）-2-（羧基环丙基）甘氨酸（L-CCG-I）可保护混合培养物中生长的小鼠皮质神经元，使其免受由 10 分钟 NMDA 脉冲诱导的兴奋性毒性退变。不仅当激动剂与 NMDA 联合添加时观察到保护作用，而且当它们在 NMDA 脉冲前 6 - 20 小时短暂应用于培养物时也观察到保护作用。在这两种情况下，II 型 mGlu 受体拮抗剂（2S,1'S,2'S,3'R）-2-（2'-羧基-3'-苯基环丙基）甘氨酸（PCCG-IV）以及蛋白质合成抑制剂环己酰亚胺（CHX）均可降低神经保护作用。混合培养物中的神经元和星形胶质细胞均用一种可识别重组细胞中 mGlu2 和 mGlu3 受体的抗体进行免疫染色。为了确定星形胶质细胞在 II 型 mGlu 受体介导的神经保护中是否发挥任何作用，我们将皮质星形胶质细胞的纯培养物暴露于 DCG-IV、4C3HPG 或 L-CCG-I 中 10 分钟。在暴露于这些药物中的任何一种后 2 - 20 小时收集的星形胶质细胞培养基，当转移至用 NMDA 处理的混合培养物中时具有高度神经保护作用。当在短暂暴露于 II 型 mGlu 受体激动剂后立即将 CHX 应用于星形胶质细胞培养物时，这种保护活性降低。我们得出结论，培养的皮质细胞中 II 型 mGlu 受体介导的神经保护需要新的蛋白质合成，并且涉及神经元与星形胶质细胞之间的相互作用。
