Leuchtmann Elizabeth A, Ratner Andrea E, Vijitruth Rattanavijit, Qu Yun, McDonald John W
Center for the Study of Nervous System Injury, Washington University School of Medicine, Box 8518, St. Louis, MO 63108, USA.
Neurobiol Dis. 2003 Dec;14(3):336-48. doi: 10.1016/j.nbd.2003.07.004.
Myelination of axons is important for central nervous system function, but oligodendrocytes, which constitute CNS myelin, are vulnerable to excitotoxic injury and death. Although mature oligodendrocytes express functional alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) and kainate-type glutamate receptors, the relative roles of these subtypes in excitotoxicity are not well understood. Using recently developed selective antagonists for subtypes of ionotropic non-NMDA receptors, we addressed this issue. By examining the pharmacological, biochemical, and morphologic features of kainite-induced excitotoxic death, we also determined whether it occurs by apoptosis, necrosis, or both. We conclude that when mature oligodendrocytes die after exposure to kainate: (1) AMPA receptors are the most important mediators, (2) kainate receptors play a smaller role, and (3) death occurs predominantly by necrosis, not apoptosis.
轴突的髓鞘形成对中枢神经系统功能很重要，但构成中枢神经系统髓鞘的少突胶质细胞易受兴奋性毒性损伤和死亡影响。尽管成熟的少突胶质细胞表达功能性的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和海人酸型谷氨酸受体，但这些亚型在兴奋性毒性中的相对作用尚未得到充分了解。我们使用最近开发的离子型非NMDA受体亚型的选择性拮抗剂来解决这个问题。通过研究海人酸诱导的兴奋性毒性死亡的药理学、生化和形态学特征，我们还确定了它是通过凋亡、坏死还是两者兼而有之发生的。我们得出结论，当成熟的少突胶质细胞在接触海人酸后死亡时：（1）AMPA受体是最重要的介质，（2）海人酸受体起的作用较小，（3）死亡主要通过坏死而非凋亡发生。
