Chronic zinc exposure decreases the surface expression of NR2A-containing NMDA receptors in cultured hippocampal neurons.
Chronic zinc exposure decreases the surface expression of NR2A-containing NMDA receptors in cultured hippocampal neurons.
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长期接触锌会降低培养海马神经元中含有 NR2A 的 NMDA 受体的表面表达
DOI：
10.1371/journal.pone.0046012
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Shen Y
中科院分区：
文献类型：
--
作者：
Zhu J;Shao CY;Yang W;Zhang XM;Wu ZY;Zhou L;Wang XX;Li YH;Xia J;Luo JH;Shen Y
研究背景锌在中枢神经系统中分布广泛，尤其是海马、杏仁核和皮质。锌的动态平衡对神经元功能至关重要。锌通过直接抑制和多种细胞内信号通路调节N-甲基-D-天冬氨酸受体（NMDAR）的活性。异常的NMDAR活性与许多脑疾病的病因学有关。已知细胞外液中持续的锌积累与病理状况有关。然而，这种慢性锌暴露和NMDAR功能障碍的机制知之甚少。方法/主要发现我们报道，慢性锌暴露减少NR 1和NR 2A集群在培养的海马锥体神经元的数量。全细胞和突触NR 2A介导的电流也减少。相比之下，锌不影响NR 2B，表明慢性锌暴露特别影响NR 2A-含NMDAR。表面生物素化表明，锌暴露减弱了NR 1和NR 2A的膜表达，这可能是由于NR 2A-PSD-95-Src复合物的解离。结论慢性锌暴露可干扰海马神经元NR 2A与PSD-95的相互作用，导致海马神经元NMDAR活性紊乱，提示锌对海马神经元NMDAR活性的影响不同于急性锌暴露。
Background Zinc distributes widely in the central nervous system, especially in the hippocampus, amygdala and cortex. The dynamic balance of zinc is critical for neuronal functions. Zinc modulates the activity of N-methyl-D-aspartate receptors (NMDARs) through the direct inhibition and various intracellular signaling pathways. Abnormal NMDAR activities have been implicated in the aetiology of many brain diseases. Sustained zinc accumulation in the extracellular fluid is known to link to pathological conditions. However, the mechanism linking this chronic zinc exposure and NMDAR dysfunction is poorly understood. Methodology/Principal Findings We reported that chronic zinc exposure reduced the numbers of NR1 and NR2A clusters in cultured hippocampal pyramidal neurons. Whole-cell and synaptic NR2A-mediated currents also decreased. By contrast, zinc did not affect NR2B, suggesting that chronic zinc exposure specifically influences NR2A-containg NMDARs. Surface biotinylation indicated that zinc exposure attenuated the membrane expression of NR1 and NR2A, which might arise from to the dissociation of the NR2A-PSD-95-Src complex. Conclusions Chronic zinc exposure perturbs the interaction of NR2A to PSD-95 and causes the disorder of NMDARs in hippocampal neurons, suggesting a novel action of zinc distinct from its acute effects on NMDAR activity.
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影响因子：
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