Glutamate-mediated excitotoxicity in neonatal hippocampal neurons is mediated by mGluR-induced release of Ca++ from intracellular stores and is prevented by estradiol
Glutamate-mediated excitotoxicity in neonatal hippocampal neurons is mediated by mGluR-induced release of Ca++ from intracellular stores and is prevented by estradiol
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DOI：
10.1111/j.1460-9568.2006.05189.x
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发表时间：
2006-12-01
影响因子：
3.4
通讯作者：
McCarthy, Margaret M.
中科院分区：
文献类型：
--
作者：
Hilton, Genell D.;Nunez, Joseph L.;McCarthy, Margaret M.
新生儿、足月儿和早产儿的缺氧缺氧性脑损伤是认知和运动功能终生障碍的常见和普遍来源。在成人中，HI通过激活NMDA受体诱导谷氨酸释放和兴奋性毒性细胞死亡。在早产儿的动物模型中，缺氧缺血后也会释放谷氨酸，但神经元对NMDA或AMPA/海人藻酸(KA)受体介导的损伤基本不敏感。利用原代培养的海马神经元，我们已经确定谷氨酸比海藻酸增加细胞内钙的作用要大得多。此外，谷氨酸通过激活I型代谢型谷氨酸受体(MGluRs)诱导细胞死亡。用性腺类固醇雌二醇预处理神经元可降低I型代谢型谷氨酸受体的水平，并完全防止细胞死亡，提示了一种治疗新生儿兴奋性中毒性脑损伤的新方法。
Hypoxic/ischernic (HI) brain injury in newborn full-term and premature infants is a common and pervasive source of life time disabilities in cognitive and locomotor function. In the adult, HI induces glutamate release and excitotoxic cell death dependent on NMDA receptor activation. In animal models of the premature human infant, glutamate is also released following HI, but neurons are largely insensitive to NMDA or AMPA/kainic acid (KA) receptor-mediated damage. Using primary cultured hippocampal neurons we have determined that glutamate increases intracellular calcium much more than kainic acid. Moreover, glutamate induces cell death by activating Type I metabotropic glutamate receptors (mGluRs). Pretreatment of neurons with the gonadal steroid estradiol reduces the level of the Type I metabotropic glutamate receptors and completely prevents cell death, suggesting a novel therapeutic approach to excitotoxic brain damage in the neonate.