Glutamate receptor expression and chronic glutamate toxicity in rat motor cortex.
Glutamate receptor expression and chronic glutamate toxicity in rat motor cortex.
复制标题
大鼠运动皮层谷氨酸受体表达和慢性谷氨酸毒性。
DOI：
10.1016/j.nbd.2006.12.002
复制
发表时间：
2007
影响因子：
6.1
通讯作者：
Brorson,JamesR
中科院分区：
文献类型：
--
作者：
Young,KateC;McGehee,DanielS;Brorson,JamesR
除了脊髓运动神经元的丧失外，肌萎缩侧索硬化症（ALS）还与皮质脊髓V层锥体神经元变性和皮层谷氨酸转运减少有关。我们在急性分离的大鼠运动皮层切片中表征了皮质脊髓神经元上的谷氨酸受体，发现相对于AMPA受体，NMDA受体对皮质脊髓V层神经元的突触输入的比例贡献小于II/III层锥体神经元。在皮层器官型切片培养模型中，阻断谷氨酸转运蛋白会使介质中的谷氨酸升高，并导致两层的锥体神经元丢失。AMPA/kainate或Ca2+渗透性AMPA受体拮抗剂可减轻V层锥体神经元的损失，提示其在ALS患者的运动皮质保护中具有治疗潜力。
In addition to the loss of spinal motor neurons, amyotrophic lateral sclerosis (ALS) is also associated with degeneration of corticospinal layer V pyramidal neurons and decreased glutamate transport in the cortex. We characterized the glutamate receptors on corticospinal neurons in acutely isolated rat motor cortex slices and found that the synaptic inputs to the corticospinal layer V neurons had a lesser proportional contribution from NMDA receptors relative to AMPA receptors than did layer II/III pyramidal neurons. The synaptic IAMPAwas also more inwardly rectified, indicating a greater Ca2+-permeable component, in layer V. In a cortical organotypic slice culture model, blockade of glutamate transporters elevated glutamate in the media and led to pyramidal neuron loss in both layers. The loss of layer V pyramidal neurons was attenuated by antagonists of AMPA/kainate or Ca2+-permeable AMPA receptors, suggesting their therapeutic potential in the protection of the motor cortex in ALS.