Increased sensitivity to NMDA is involved in alcohol-withdrawal induced cytotoxicity observed in primary cultures of cortical neurones chronically pre-treated with ethanol
Increased sensitivity to NMDA is involved in alcohol-withdrawal induced cytotoxicity observed in primary cultures of cortical neurones chronically pre-treated with ethanol
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DOI：
10.1016/s0197-0186(01)00131-0
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发表时间：
2002-06-01
影响因子：
4.2
通讯作者：
László, L
中科院分区：
文献类型：
--
作者：
Nagy, J;László, L
严重的细胞损伤和神经元细胞丢失以前观察到在培养初级皮质神经元后，慢性乙醇预处理和乙醇退出。在这项研究中，我们调查了导致酒精戒断诱导的神经元细胞死亡的情况和可能的细胞变化。当文化与乙醇预处理(25 - 200毫米)一次24或72 h,随后的24小时的酒精诱导细胞death-estimated通过测量乳酸脱氢酶(LDH)的释放是只有在文化与200毫米乙醇预处理72 h。相反,只有50毫米乙醇产生显著增加(P < 0.01)撤军诱导LDH-release文化与乙醇预处理的反复连续三天每天一次。当在停药期间将乙醇重新添加到培养物中时，ldl释放量呈剂量依赖性地降低到对照水平。在乙醇预处理培养物中，n -甲基- d -天冬氨酸（NMDA） （0.01-1 mM）诱导兴奋毒性，并引起胞浆钙离子浓度升高。相反，去极化剂veratridine （0.01-1 mM）在对照组中产生了与乙醇预处理培养相似的神经元损伤程度和胞质钙离子浓度升高。根据这些观察，重复乙醇处理似乎在培养的神经元中引起更强的适应性变化，导致比慢性单次处理更明显的戒断诱导的细胞损伤。此外，谷氨酸能神经传递，特别是NMDA受体系统似乎高度参与了酒精戒断的适应性变化和细胞毒性作用。(C) 2002 Elsevier Science Ltd.版权所有。
Severe cellular damage and neuronal cell loss were previously observed in cultures of primary cortical neurones after chronic ethanol pre-treatment followed by ethanol-withdrawal. In this study, we investigated the circumstances and the possible cellular changes leading to alcohol-withdrawal induced neuronal cell death. When cultures were pre-treated with ethanol (25-200 mM) once for 24 or 72 h, the amount of the subsequent 24 h alcohol-withdrawal induced cell death-estimated by measuring the release of lactate dehydrogenase (LDH)- was elevated only in cultures pre-treated with 200 mM ethanol for 72 h. On the contrary, as little as 50 mM ethanol produced significant (P < 0.01) increase in the withdrawal induced LDH-release in cultures pre-treated repeatedly with ethanol once daily for three consecutive days. When ethanol was re-added to the cultures during the withdrawal period, the LDH-release was dose-dependently reduced to the level of control. In ethanol pre-treated cultures N-methyl-D-aspartate (NMDA) (0.01-1 mM) induced excitotoxicity as well as NMDA evoked elevation of cytosolic calcium ion concentration was increased. In contrast, the depolarising agent veratridine (0.01-1 mM) produced similar extent of neuronal injury and elevation in cytosolic calcium ion concentration in control as in ethanol pre-treated cultures. According to these observations, repeated ethanol treatment appears to cause more robust adaptive changes in cultured neurones leading to more pronounced withdrawal induced cellular damage than chronic but single treatment does. In addition, the glutamatergic neurotransmission, especially the NMDA receptor system seems to be highly involved in the adaptive changes and in the cytotoxic effect of alcohol-withdrawal. (C) 2002 Elsevier Science Ltd. All rights reserved.