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NMDA receptors are expressed in oligodendrocytes and activated in ischaemia

机译:NMDA受体在少突胶质细胞中表达并在缺血中被激活

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Glutamate-mediated damage to oligodendrocytes contributes to mental or physical impairment in periventricular leukomalacia (pre- or perinatal white matter injury leading to cerebral palsy), spinal cord injury, multiple sclerosis and stroke. Unlike neurons, white matter oligodendrocytes reportedly lack NMDA (N-methyl-D-aspartate) receptors. It is believed that glutamate damages oligodendrocytes, especially their precursor cells, by acting on calcium-permeable AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)/kainate receptors alone or by reversing cystine-glutamate exchange and depriving cells of antioxidant protection. Here we show that precursor, immature and mature oligodendrocytes in the white matter of the cerebellum and corpus callosum exhibit NMDA-evoked currents, mediated by receptors that are blocked only weakly by Mg~(2+) and that may contain NR1, NR2C and NR3 NMDA receptor subunits. NMDA receptors are present in the myelinating processes of oligodendrocytes, where the small intracellular space could lead to a large rise in intracellular ion concentration in response to NMDA receptor activation. Simulating ischaemia led to development of an inward current in oligodendrocytes, which was partly mediated by NMDA receptors. These results point to NMDA receptors of unusual subunit composition as a potential therapeutic target for preventing white matter damage in a variety of diseases.
机译:谷氨酸介导的少突胶质细胞损害会导致脑室白细胞软化症(导致脑瘫的产前或围产期白质损伤),脊髓损伤,多发性硬化和中风的精神或身体损害。据报道,与神经元不同,白质少突胶质细胞缺乏NMDA(N-甲基-D-天冬氨酸)受体。据信谷氨酸通过单独作用于钙可渗透的AMPA(α-氨基-3-羟基-5-甲基-5-甲基-4-异恶唑丙酸)/海藻酸酯受体或通过逆转胱氨酸-谷氨酸交换来破坏少突胶质细胞,特别是其前体细胞。剥夺细胞的抗氧化保护能力在这里我们显示小脑和体白质中的前体,未成熟和成熟的少突胶质细胞表现出NMDA诱发的电流,该电流由仅被Mg〜(2+)弱阻断的受体介导,并且可能含有NR1,NR2C和NR3 NMDA受体亚基。 NMDA受体存在于少突胶质细胞的髓鞘形成过程中,其中较小的细胞内空间可能会响应NMDA受体激活而导致细胞内离子浓度大幅上升。模拟局部缺血导致少突胶质细胞内向电流的发展,其部分由NMDA受体介导。这些结果表明,具有异常亚基组成的NMDA受体是预防各种疾病中白质损害的潜在治疗靶标。

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