The effect of N-acetyl-aspartyl-glutamate and N-acetyl-aspartate on white matter oligodendrocytes.
The effect of N-acetyl-aspartyl-glutamate and N-acetyl-aspartate on white matter oligodendrocytes.
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DOI：
10.1093/brain/awp087
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发表时间：
2009-06
期刊：
影响因子：
--
通讯作者：
Attwell D
中科院分区：
文献类型：
--
作者：
Kolodziejczyk K;Hamilton NB;Wade A;Káradóttir R;Attwell D
N-乙酰基-天冬氨酰-谷氨酸 (NAAG) 和 N-乙酰基-天冬氨酸 (NAA) 水平升高与脑白质营养不良 Canavan 病和 Pelizaeus-Merzbacher 样病中的髓鞘质损失有关。 NAAG和NAA可以激活和拮抗神经元N-甲基-D-天冬氨酸(NMDA)受体，并且还作用于II族代谢型谷氨酸受体。最近显示少突胶质细胞及其前体细胞表达 NMDA 受体，缺血时这些受体的激活导致少突胶质细胞前体细胞死亡和髓鞘质损失。这提出了一种可能性，即脑白质营养不良中发生的髓磷脂发育失败或脱髓鞘可能反映了 NAAG 或 NAA 对少突胶质细胞 NMDA 受体的作用。然而，由于少突胶质细胞上 NMDA 受体的假定亚基组成与神经元 NMDA 受体不同，因此 NAAG 和 NAA 对它们的影响尚不清楚。我们发现，NAAG（而不是 NAA）会在小脑白质少突胶质细胞中引起内向膜电流，该电流会因 NMDA 受体阻断（但不会因代谢型谷氨酸受体阻断）而减少。相对于 NMDA 引起的电流，NAAG 引起的电流大小在少突胶质细胞中比在神经元中小得多，并且 NAAG 诱导神经元中的 [Ca2+]i 升高，但在少突胶质细胞中则不然。 NAAG 对少突胶质细胞和神经元的影响的这些差异可能反映了受体亚基组成的上述差异。此外，由于少突胶质细胞反应的主要部分被河豚毒素 (TTX) 阻断，少突胶质细胞中的大部分 NAAG 诱发电流是激活神经元 NMDA 受体的次要结果。暴露于 1 mM NAAG 六小时不会导致白质细胞死亡。我们得出的结论是，NAAG 对少突胶质细胞 NMDA 受体的作用不太可能是白质营养不良中白质损伤的主要原因。
Elevations of the levels of N-acetyl-aspartyl-glutamate (NAAG) and N-acetyl-aspartate (NAA) are associated with myelin loss in the leucodystrophies Canavan's disease and Pelizaeus-Merzbacher-like disease. NAAG and NAA can activate and antagonize neuronal N-methyl-D-aspartate (NMDA) receptors, and also act on group II metabotropic glutamate receptors. Oligodendrocytes and their precursors have recently been shown to express NMDA receptors, and activation of these receptors in ischaemia leads to the death of oligodendrocyte precursors and the loss of myelin. This raises the possibility that the failure to develop myelin, or demyelination, occurring in the leucodystrophies could reflect an action of NAAG or NAA on oligodendrocyte NMDA receptors. However, since the putative subunit composition of NMDA receptors on oligodendrocytes differs from that of neuronal NMDA receptors, the effects of NAAG and NAA on them are unknown. We show that NAAG, but not NAA, evokes an inward membrane current in cerebellar white matter oligodendrocytes, which is reduced by NMDA receptor block (but not by block of metabotropic glutamate receptors). The size of the current evoked by NAAG, relative to that evoked by NMDA, was much smaller in oligodendrocytes than in neurons, and NAAG induced a rise in [Ca2+]i in neurons but not in oligodendrocytes. These differences in the effect of NAAG on oligodendrocytes and neurons may reflect the aforementioned difference in receptor subunit composition. In addition, as a major part of the response in oligodendrocytes was blocked by tetrodotoxin (TTX), much of the NAAG-evoked current in oligodendrocytes is a secondary consequence of activating neuronal NMDA receptors. Six hours exposure to 1 mM NAAG did not lead to the death of cells in the white matter. We conclude that an action of NAAG on oligodendrocyte NMDA receptors is unlikely to be a major contributor to white matter damage in the leucodystrophies.
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影响因子：
3.3
作者：
DANGELO, E;ROSSI, P;TAGLIETTI, V
通讯作者：
TAGLIETTI, V
影响因子：
7.6
作者：
Bergeron, R;Coyle, JT;Greene, RW
通讯作者：
Greene, RW
影响因子：
4.2
作者：
JAKOBS, C;TENBRINK, HJ;KLEIJER, WJ
通讯作者：
KLEIJER, WJ
影响因子：
64.8
作者：
Salter, MG;Fern, R
通讯作者：
Fern, R
将脑切片中细胞的膜片钳与免疫细胞化学标记相结合，以确定细胞类型和发育阶段。
影响因子：
14.8
作者：
Karadottir, Ragnhildur;Attwell, David
通讯作者：
Attwell, David