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首页> 外文期刊>Brain research >Memantine attenuates staurosporine-induced activation of caspase-3 and LDH release in mouse primary neuronal cultures.
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Memantine attenuates staurosporine-induced activation of caspase-3 and LDH release in mouse primary neuronal cultures.

机译：美金刚胺减弱了星形孢菌素诱导的小鼠原代神经元培养物中caspase-3和LDH释放的激活。

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Developmental aspects of pro- and antiapoptotic action of some NMDA receptor antagonists in the central nervous system have been postulated. In order to further elucidate this problem, we investigated effect of memantine, an uncompetitive NMDA receptor antagonist and staurosporine alone and in combination on caspase-3 activity and lactate dehydrogenase (LDH) release in primary hippocampal, neocortical and striatal cell cultures on 7 and 12 days in vitro. The data showed that the vulnerability of neuronal cells to induction of caspase-3 activity by staurosporine was higher on 7 DIV than on 12 DIV, whereas staurosporine-mediated LDH release increased with days in vitro in striatal culture only. A specific inhibitor of caspase-3, AcDEVDCHO (60 muM), completely abolished the effect of staurosporine on this enzyme's activity, but only partially attenuated staurosporine-induced LDH release in hippocampal cells. Memantine alone (0.05-2.0 muM) did not induce any cytototoxic effect but attenuated the staurosporine-induced caspase-3 activity and LDH release in hippocampal cultured neurons on each investigated day in vitro. In striatal culture, memantine had a moderate inhibitory effect on staurosporine-evoked LDH release only on 7 DIV with no significant influence on caspase-3 activity. As for neocortical cultures, memantine partially inhibited staurosporine-induced neuronal injury only on 7 DIV. These data showed that the induction of caspase-3 activity by staurosporine was more profound in immature cells, however, the staurosporine neurotoxicity, as reflected by LDH release, only partially depended on caspase-3 activation and stage of cell development. Furthermore, memantine attenuated staurosporine-induced apoptosis more efficiently in hippocampal cultures than in neocortical and striatal ones, which points to tissue specificity of effects of this neuroprotectant.
机译：假定某些NMDA受体拮抗剂在中枢神经系统中具有促凋亡和抗凋亡作用。为了进一步阐明这个问题，我们研究了美金刚，一种非竞争性NMDA受体拮抗剂和星形孢菌素的组合，以及它们对原代海马，新皮层和纹状体细胞培养物中caspase-3活性和乳酸脱氢酶（LDH）释放的影响，分别针对7和12体外天数。数据显示，在7 DIV上神经元细胞对星形孢菌素诱导caspase-3活性的敏感性高于在12 DIV上，而星形孢菌素介导的LDH释放仅在体外纹状体培养中随天数增加。一种特定的caspase-3抑制剂AcDEVDCHO（60μM）完全消除了星形孢菌素对该酶活性的影响，但仅部分减弱了星形孢菌素诱导的LDH在海马细胞中的释放。单独的美金刚胺（0.05-2.0μM）不会诱导任何细胞毒性作用，但在体外每个研究日中，都会减弱星形孢菌素诱导的caspase-3活性和LDH在海马培养的神经元中的释放。在纹状体培养中，美金刚胺仅在7 DIV上对星形孢菌素诱发的LDH释放具有中等抑制作用，而对caspase-3活性无明显影响。至于新皮质培养，美金刚胺仅在7 DIV时部分抑制星形孢菌素诱导的神经元损伤。这些数据表明，在未成熟细胞中，星形孢菌素对caspase-3活性的诱导作用更为明显，但是，由LDH释放所反映的星形孢菌素神经毒性仅部分取决于caspase-3的活化和细胞发育阶段。此外，美金刚胺在海马培养物中比新皮层和纹状体培养物中更有效地减轻了星形孢菌素诱导的凋亡，这表明该神经保护剂作用的组织特异性。

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