在化学缺血期间,NMDA受体调解了髓中的积累
1Ottawa Health Research Institute, Division of Neuroscience and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1Y 4K9, Canada.
Nature
|December 24, 2005
概括
中枢神经系统的髓可以在缺血期间积累,独立于寡细胞. 髓中的N-甲基-d-酸盐 (NMDA) 受体调解了这种的增加,这表明在脱髓化疾病中是一种新的治疗标.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 神经退行发生神经退行.
背景情况:
- 中枢神经系统 (CNS) 的髓由寡细胞产生,对快速的神经冲动传导至关重要.
- 髓损伤和损失是许多神经系统疾病的标志,导致严重的残疾.
- 启动髓损伤的机制尚不清楚,通常认为它反映了寡细胞的命运.
研究的目的:
- 调查N-甲基-d-酸盐 (NMDA) 谷氨酸受体在化学缺血期间中枢神经系统髓质内积累中介的作用.
- 为了确定髓是否可以独立地对有害刺激作出反应.
- 探索脱髓化疾病的潜在治疗点.
主要方法:
- 利用双光子显微镜对成年老鼠视神经中的指标X-rhod-1进行成像.
- 应用了各种NMDA和AMPA/酸盐受体对抗剂 (MK-801,7-氨酸,d-AP5,NBQX,NVP-AAM077,ifenprodil).
- 进行了免疫组织化学和免疫沉,以检测髓蛋白中的NMDA受体子单元 (NR1,NR2,NR3).
主要成果:
- NMDA受体对抗剂,但不是AMPA/甲酸盐对抗剂,显著阻断了缺血引起的髓增加.
- 通过NMDA受体对抗,可以显著降低因体外缺血引起的髓超结构性损伤.
- 在髓中检测到所有必要的NMDA受体子单元,表明功能性受体存在.
结论:
- 成熟的髓膜可以响应有害的刺激,如缺血,独立于母寡细胞.
- 位于髓外内的NMDA受体在缺血期间调节的积累,代表了一种新的轴骨髓信号通路.
- 向髓质NMDA受体为多发性硬化症和神经创伤等脱髓化疾病提供了潜在的治疗策略.
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