Lack of Correlation Between the Effects of Transient Exposure to Glutamate and Those of Hypoxia/Reoxygenation in Immature Neurons In Vitro
Lack of Correlation Between the Effects of Transient Exposure to Glutamate and Those of Hypoxia/Reoxygenation in Immature Neurons In Vitro
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体外短暂暴露于谷氨酸的影响与未成熟神经元缺氧/复氧的影响之间缺乏相关性
DOI：
10.1046/j.1471-4159.1998.71031177.x
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发表时间：
1998
影响因子：
4.7
通讯作者：
J. Daval
中科院分区：
文献类型：
--
作者：
R. Chihab;C. Bossenmeyer;J. Oillet;J. Daval
摘要：为了评估大脑不成熟对缺氧效应的影响和兴奋性毒性的参与，在两个成熟阶段（即，体外培养6天和13天。检查细胞的形态、活力、通过2-d-[3 H]脱氧葡萄糖摄取反映的能量代谢和通过[3 H]亮氨酸掺入评估的蛋白质合成。使用荧光染料4，6-diamidino-2-phenylindole对细胞凋亡和坏死进行评分。而6天龄的神经元对6小时缺氧的反应是短暂的高代谢，蛋白质合成的双相增加，以及暴露后72小时内的放线菌酮敏感性凋亡死亡，谷氨酸在同一时间没有影响细胞特性。在13天龄的神经元中，缺氧诱导凋亡（8.2%）和坏死（22.3%）。在这个年龄段，谷氨酸在暴露结束时肯定会降低能量代谢（26%）和蛋白质合成（17%）。神经元坏死率达40.7%，而凋亡率与对照组相比无明显变化。因此，兴奋性毒性不能解释未成熟神经元中缺氧诱导的损伤，但在13天时谷氨酸受体拮抗剂对缺氧坏死成分的抑制表明其参与了老化细胞。
Abstract: To assess the influence of brain immaturity on the effects of oxygen deprivation and the participation of excitotoxicity, the consequences of a 6‐h exposure to either hypoxia (95% N2/5% CO2) or 100 µM glutamate were studied in cultured fetal rat forebrain neurons taken at two maturational stages, i.e., 6 and 13 days in vitro. Cells were examined for their morphology, viability, energy metabolism reflected by 2‐d‐[3H]deoxyglucose uptake, and protein synthesis assessed by [3H]leucine incorporation. Apoptosis and necrosis were scored using the fluorescent dye 4,6‐diamidino‐2‐phenylindole. Whereas 6‐day‐old neurons responded to a 6‐h hypoxia by transient hypermetabolism, biphasic increase in protein synthesis, and cycloheximide‐sensitive apoptotic death within 72 h postexposure, glutamate did not affect cell characteristics by the same time. In 13‐day‐old neurons, hypoxia induced both apoptosis (8.2%) and necrosis (22.3%). At this age, glutamate definitely reduced energy metabolism (26%) and protein synthesis (17%) by the end of exposure. The percentage of necrotic neurons reached 40.7%, but the rate of apoptosis was unchanged compared with controls. Therefore, excitotoxicity cannot account for hypoxia‐induced injury in immature neurons, but its participation is suggested in older cells by the suppression of the necrotic component of hypoxia by glutamate receptor antagonists at 13 days.
影响因子：
56.9
作者：
KAKU, DA;GIFFARD, RG;CHOI, DW
通讯作者：
CHOI, DW
影响因子：
13.5
作者：
C. Zorumski;J. Olney
通讯作者：
C. Zorumski;J. Olney