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首页> 外文期刊>The European Journal of Neuroscience >Brief exposure to NMDA produces long-term protection of cerebellar granule cells from apoptosis.
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Brief exposure to NMDA produces long-term protection of cerebellar granule cells from apoptosis.

机译：短暂暴露于NMDA可以长期保护小脑颗粒细胞免于凋亡。

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摘要

Cerebellar granule cells (CGCs) require excitatory inputs to survive during their postnatal migration from the external to the internal granule cell layers. The lack of innervation of mossy fibres induces CGC death by apoptosis. In vitro, CGCs die by apoptosis in the presence of physiological concentrations of KCl (5 mm or K5) but they survive in the presence of depolarizing concentrations of KCl (25 mm or K25) or N-methyl-d-aspartate (NMDA) by a mechanism dependent on calcium influx. The addition of NMDA or K25, for only 24 h, to immature CGCs cultures [2 days in vitro (DIV)] was able to produce a remarkable and long-term protection until 8 DIV. Moreover, our data show that NMDA and K25-mediated long-lasting protection was related to an inhibition of caspase-3 activity. By using different protein kinase inhibitors, we have shown that the inhibition of caspase-3 activation by NMDA was dependent on the activation of tyrosine kinases and phosphatidylinositol 3-kinase (PI3-kinase). Moreover, an impairmentin NMDA-mediated neuroprotection and caspase-3 inhibition was observed when the action of brain-derived neurotrophic factor (BDNF) was blocked. By contrast, K25-mediated neuroprotection was BDNF-independent and was mediated by a mitogen-activated protein kinase- and PI3-kinase-dependent inhibition of caspase-3.
机译：小脑颗粒细胞（CGC）需要刺激性输入才能在出生后从外部颗粒层迁移到内部颗粒细胞层时存活。缺少苔藓纤维的神经支配会诱导CGC通过凋亡而死亡。在体外，CGC在生理浓度的KCl（5 mm或K5）存在下通过凋亡而死亡，但在去极化浓度的KCl（25 mm或K25）或N-甲基-d-天门冬氨酸（NMDA）存在下存活。一种依赖钙流入的机制。向未成熟的CGC培养物中添加NMDA或K25仅24小时[体外2天（DIV）]即可产生显着且长期的保护，直至8 DIV。此外，我们的数据表明NMDA和K25介导的持久保护与caspase-3活性的抑制有关。通过使用不同的蛋白激酶抑制剂，我们已经表明NMDA对caspase-3激活的抑制作用取决于酪氨酸激酶和磷脂酰肌醇3激酶（PI3激酶）的激活。此外，当脑源性神经营养因子（BDNF）的作用被阻滞时，观察到NMDA介导的损伤保护和caspase-3抑制。相比之下，K25介导的神经保护作用是BDNF依赖性的，并且是由有丝分裂原激活的蛋白激酶和PI3激酶依赖性的caspase-3抑制介导的。

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