Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, Poland.
Int J Mol Sci. 2019 Jan 14;20(2):309. doi: 10.3390/ijms20020309.
Studies of the last two decades have demonstrated the presence in astrocytic cell membranes of -methyl-d-aspartate (NMDA) receptors (NMDARs), albeit their apparently low abundance makes demonstration of their presence and function more difficult than of other glutamate (Glu) receptor classes residing in astrocytes. Activation of astrocytic NMDARs directly in brain slices and in acutely isolated or cultured astrocytes evokes intracellular calcium increase, by mutually unexclusive ionotropic and metabotropic mechanisms. However, other than one report on the contribution of astrocyte-located NMDARs to astrocyte-dependent modulation of presynaptic strength in the hippocampus, there is no sound evidence for the significant role of astrocytic NMDARs in astrocytic-neuronal interaction in neurotransmission, as yet. Durable exposure of astrocytic and neuronal co-cultures to NMDA has been reported to upregulate astrocytic synthesis of glutathione, and in this way to increase the antioxidative capacity of neurons. On the other hand, overexposure to NMDA decreases, by an as yet unknown mechanism, the ability of cultured astrocytes to express glutamine synthetase (GS), aquaporin-4 (AQP4), and the inward rectifying potassium channel Kir4.1, the three astroglia-specific proteins critical for homeostatic function of astrocytes. The beneficial or detrimental effects of astrocytic NMDAR stimulation revealed in the in vitro studies remain to be proven in the in vivo setting.
过去二十年的研究表明，星形胶质细胞膜上存在 -甲基-D-天冬氨酸（NMDA）受体（NMDARs），尽管其明显的低丰度使得证明其存在和功能比其他驻留在星形胶质细胞中的谷氨酸（Glu）受体更为困难。在脑切片中直接激活星形胶质细胞 NMDAR 以及在急性分离或培养的星形胶质细胞中，通过相互非离子型和代谢型机制引起细胞内钙增加。然而，除了一份关于星形胶质细胞定位的 NMDAR 对海马体中星形胶质细胞依赖性调节突触前强度的贡献的报告外，目前尚无确凿证据表明星形胶质细胞 NMDAR 在神经递质传递中的星形胶质细胞-神经元相互作用中发挥重要作用。据报道，星形胶质细胞和神经元共培养物持续暴露于 NMDA 会上调星形胶质细胞谷胱甘肽的合成，从而增加神经元的抗氧化能力。另一方面，过度暴露于 NMDA 会以未知的机制降低培养的星形胶质细胞表达谷氨酰胺合成酶（GS）、水通道蛋白-4（AQP4）和内向整流钾通道 Kir4.1 的能力，这三种星形胶质细胞特异性蛋白对星形胶质细胞的稳态功能至关重要。在体外研究中揭示的星形胶质细胞 NMDAR 刺激的有益或有害影响仍有待在体内环境中证明。
