Neuroprotective role of δ-opioid receptors in cortical neurons
Neuroprotective role of δ-opioid receptors in cortical neurons
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DOI：
10.1152/ajpcell.00226.2001
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发表时间：
2002-06-01
影响因子：
5.5
通讯作者：
Xia, Y
中科院分区：
文献类型：
--
作者：
Zhang, JH;Gibney, GT;Xia, Y
我们最近证明了delta-阿片受体（DOR）的激活可以保护皮质神经元免受谷氨酸诱导的损伤。由于谷氨酸是神经元缺氧损伤的介质，我们假设DOR参与O-2剥夺期间的神经保护，其激活/抑制可能改变神经元对缺氧应激的易感性。在这项工作中，我们测试了缺氧（1% O2）下阿片受体激活和抑制对培养皮层神经元的影响。通过乳酸脱氢酶释放、基于形态学的定量和活/死染色来评估细胞损伤。结果表明：1)未成熟神经元（第4天和第6天）在缺氧72 h后才受到明显损伤，而第8天的神经元仅在缺氧24 h后就受到损伤；2) DOR抑制（纳曲多）在正常培养的第4天和第8天均引起神经元损伤，并进一步增强了这些神经元的缺氧损伤；3) DOR激活([D-Ala（2), D-Leu(5)]脑啡肽）在正常或低氧暴露24小时后减少了第8天培养的神经元损伤，并随着暴露时间的延长减轻了纳trindole引起的损伤；4) mu-或kappa-阿片受体抑制（-funaltrexamine或norbinaltorphimine）在常氧或缺氧条件下对神经元的影响很小。总的来说，这些数据表明DOR在常氧和缺氧环境下的神经保护中起着至关重要的作用。
We recently demonstrated that delta-opioid receptor (DOR) activation protects cortical neurons against glutamate-induced injury. Because glutamate is a mediator of hypoxic injury in neurons, we hypothesized that DOR is involved in neuroprotection during O-2 deprivation and that its activation/inhibition may alter neuronal susceptibility to hypoxic stress. In this work, we tested the effect of opioid receptor activation and inhibition on cultured cortical neurons in hypoxia (1% O2). Cell injury was assessed by lactate dehydrogenase release, morphology-based quantification, and live/dead staining. Our results show that 1) immature neurons (days 4 and 6) were not significantly injured by hypoxia until 72 h of exposure, whereas day 8 neurons were injured after only 24-h hypoxia; 2) DOR inhibition (naltrindole) caused neuronal injury in both day 4 and day 8 normoxic cultures and further augmented hypoxic injury in these neurons; 3) DOR activation ([D-Ala(2), D-Leu(5)]enkephalin) reduced neuronal injury in day 8 cultures after 24 h of normoxic or hypoxic exposure and attenuated naltrindole-induced injury with prolonged exposure; and 4) mu- or kappa-opioid receptor inhibition (beta-funaltrexamine or norbinaltorphimine) had little effect on neurons in either normoxic or hypoxic conditions. Collectively, these data suggest that DOR plays a crucial role in neuroprotection in normoxic and hypoxic environments.