β-Amyloid prevents excitotoxicity via recruitment of glial glutamate transporters
β-Amyloid prevents excitotoxicity via recruitment of glial glutamate transporters
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DOI：
10.1007/s00210-003-0792-6
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发表时间：
2003-09-01
影响因子：
3.6
通讯作者：
Ikegaya, Y
中科院分区：
文献类型：
--
作者：
Baba, A;Mitsumori, K;Ikegaya, Y
β - 淀粉样蛋白（Aβ）是一种与阿尔茨海默病有关的假定致病性内毒素，它诱导星形胶质细胞中谷氨酸转运体的重新分布并促进其转运活性。由于转运体被认为可通过清除细胞外谷氨酸来保护神经元免受兴奋性毒性的影响，我们假设Aβ会改变神经元对谷氨酸的易感性。大脑皮质神经元 - 星形胶质细胞共培养物暴露于谷氨酸中，所选用的谷氨酸浓度使得只有20%的神经元出现变性。当培养物用Aβ预处理后，暴露于相同的“轻度”谷氨酸浓度下的神经元未受损伤。一种胶质谷氨酸转运体抑制剂消除了Aβ诱导的保护作用。因此，Aβ可通过谷氨酸转运体活性减轻兴奋性毒性。目前的研究结果可能会挑战Aβ诱导的神经元丢失导致阿尔茨海默病痴呆这一主流观点，同时也为谷氨酸毒性中的神经 - 胶质相互作用提供了实用的见解。
Amyloid beta-protein (Abeta), a putative pathogenic endotoxin involved in Alzheimer's disease, induces redistribution of glutamate transporters in astrocytes and promotes their pump activity. Because the transporters are assumed to protect neurons against excitotoxicity by removing extracellular glutamate, we hypothesized that Abeta alters the vulnerability of neurons to glutamate. Cerebrocortical neuron-astroglial co-cultures were exposed to glutamate, the concentration of which was selected so that only 20% of the neurons exhibited degeneration. When cultures were pre-treated with Abeta, exposure to the same 'mild' glutamate concentration failed to damage neurons. The Abeta-induced protection was abolished by a glial glutamate transporter inhibitor. Thus, Abeta can alleviate excitotoxicity through glutamate transporter activity. The present results may challenge prevailing concepts that Abeta-induced neuron loss causes Alzheimer's dementia and also provide practical insights into neuro-glial interactions in glutamate toxicity.