星形胶质细胞调节运动神经元中GluR2的表达及其对兴奋性毒性的易感性。
Astrocytes regulate GluR2 expression in motor neurons and their vulnerability to excitotoxicity.
作者信息
Van Damme Philip, Bogaert Elke, Dewil Maarten, Hersmus Nicole, Kiraly Dora, Scheveneels Wendy, Bockx Ilse, Braeken Dries, Verpoorten Nathalie, Verhoeven Kristien, Timmerman Vincent, Herijgers Paul, Callewaert Geert, Carmeliet Peter, Van Den Bosch Ludo, Robberecht Wim
机构信息
Laboratory of Neurobiology, Flanders Interuniversity Institute for Biotechnology, University of Leuven, B-3000 Leuven, Belgium.
出版信息
Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14825-30. doi: 10.1073/pnas.0705046104. Epub 2007 Sep 5.
Influx of Ca(2+) ions through alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors contributes to neuronal damage in stroke, epilepsy, and neurodegenerative disorders such as ALS. The Ca(2+) permeability of AMPA receptors is largely determined by the glutamate receptor 2 (GluR2) subunit, receptors lacking GluR2 being permeable to Ca(2+) ions. We identified a difference in GluR2 expression in motor neurons from two rat strains, resulting in a difference in vulnerability to AMPA receptor-mediated excitotoxicity both in vitro and in vivo. Astrocytes from the ventral spinal cord were found to mediate this difference in GluR2 expression in motor neurons. The presence of ALS-causing mutant superoxide dismutase 1 in astrocytes abolished their GluR2-regulating capacity and thus affected motor neuron vulnerability to AMPA receptor-mediated excitotoxicity. These results reveal a mechanism through which astrocytes influence neuronal functioning in health and disease.
通过α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）受体流入的Ca(2+)离子会导致中风、癫痫以及诸如肌萎缩侧索硬化症（ALS）等神经退行性疾病中的神经元损伤。AMPA受体的Ca(2+)通透性很大程度上由谷氨酸受体2（GluR2）亚基决定，缺乏GluR2的受体对Ca(2+)离子具有通透性。我们在两种大鼠品系的运动神经元中发现了GluR2表达的差异，这导致在体外和体内对AMPA受体介导的兴奋性毒性的易感性存在差异。发现来自腹侧脊髓的星形胶质细胞介导了运动神经元中GluR2表达的这种差异。星形胶质细胞中导致ALS的突变型超氧化物歧化酶1的存在消除了它们调节GluR2的能力，从而影响了运动神经元对AMPA受体介导的兴奋性毒性的易感性。这些结果揭示了一种星形胶质细胞在健康和疾病状态下影响神经元功能的机制。
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