Sánchez-Gómez M V, Matute C
Departamento de Neurociencias, Universidad del País Vasco, Leioa, Vizcaya, 48940, Spain.
Neurobiol Dis. 1999 Dec;6(6):475-85. doi: 10.1006/nbdi.1999.0264.
Recent studies indicate that oligodendrocytes are vulnerable to excitotoxic insults mediated by glutamate receptors. The present study was carried out to characterize the type of glutamate receptors triggering cell death in optic nerve oligodendrocyte cultures. Acute activation of either AMPA or kainate receptors was toxic to oligodendrocytes, an effect that was prevented by CNQX. However, exposure to agonists of the NMDA and metabotropic glutamate receptors did not impair cell viability. Dose-response curves showed that toxicity was mediated by three distinct populations of receptors: an AMPA-type receptor and high- and low-affinity kainate-type receptors. Expression and immunocytochemical studies suggested that the glutamate receptor subunits give rise to the native receptors in each population. In all instances, Ca(2+) entry was a major determinant of glutamate receptor excitotoxicity. However, its influence varied for each receptor subtype. These results indicate that aberrantly enhanced activation of AMPA and/or kainate receptors may be involved in demyelinating diseases.
最近的研究表明，少突胶质细胞易受谷氨酸受体介导的兴奋性毒性损伤。本研究旨在确定在视神经少突胶质细胞培养物中引发细胞死亡的谷氨酸受体类型。AMPA或海人酸受体的急性激活对少突胶质细胞有毒性，这种作用可被CNQX阻断。然而，暴露于NMDA和代谢型谷氨酸受体的激动剂并不会损害细胞活力。剂量反应曲线表明，毒性是由三种不同的受体群体介导的：一种AMPA型受体以及高亲和力和低亲和力海人酸型受体。表达和免疫细胞化学研究表明，谷氨酸受体亚基产生了每个群体中的天然受体。在所有情况下，Ca(2+)内流都是谷氨酸受体兴奋性毒性的主要决定因素。然而，其影响因每种受体亚型而异。这些结果表明，AMPA和/或海人酸受体的异常增强激活可能与脱髓鞘疾病有关。
