Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain
Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain
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DOI：
10.1126/science.283.5398.70
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发表时间：
1999-01-01
期刊：
影响因子：
56.9
通讯作者：
Olney, JW
中科院分区：
文献类型：
--
作者：
Ikonomidou, C;Bosch, F;Olney, JW
程序性细胞死亡（细胞凋亡）发生在中枢神经系统的正常发育过程中。然而，决定哪些神经元将屈服于细胞凋亡的机制知之甚少。在胎儿晚期或新生儿早期，N-甲基-D-天冬氨酸（NMDA）谷氨酸受体阻断仅几个小时，就引发了发育中的大鼠大脑中广泛的凋亡性神经变性，这表明兴奋性神经递质谷氨酸作用于NMDA受体，控制神经元的存活。这些发现可能与人类神经发育障碍有关，这些疾病涉及产前（滥用药物的母亲）或产后（儿科麻醉）暴露于阻断NMDA受体的药物。
Programmed cell death (apoptosis) occurs during normal development of the central nervous system. However, the mechanisms that determine which neurons will succumb to apoptosis are poorly understood. Blockade of N-methyl-D-aspartate (NMDA) glutamate receptors for only a few hours during late fetal or early neonatal Life triggered widespread apoptotic neurodegeneration in the developing rat brain, suggesting that the excitatory neurotransmitter glutamate, acting at NMDA receptors, controls neuronal survival. These findings may have relevance to human neurodevelopmental disorders involving prenatal (drug-abusing mothers) or postnatal (pediatric anesthesia) exposure to drugs that block NMDA receptors.