Immunogold electron microscopic evidence of differential regulation of GluN1, GluN2A, and GluN2B, NMDA-type glutamate receptor subunits in rat hippocampal CA1 synapses during benzodiazepine withdrawal.
Immunogold electron microscopic evidence of differential regulation of GluN1, GluN2A, and GluN2B, NMDA-type glutamate receptor subunits in rat hippocampal CA1 synapses during benzodiazepine withdrawal.
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DOI：
10.1002/cne.22458
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发表时间：
2010-11-01
影响因子：
2.5
通讯作者：
Tietz, Elizabeth I.
中科院分区：
文献类型：
--
作者：
Das, Paromita;Zerda, Ricardo;Alvarez, Francisco J.;Tietz, Elizabeth I.
苯二氮卓类药物戒断焦虑与大鼠海马CA 1区AMPA受体（AMPAR）介导的谷氨酸能传递有关，这是由于突触插入和GluA 1同聚体磷酸化增强所致。有趣的是，戒断焦虑的减弱与NMDA受体（NMDAR）介导的电流和亚基表达的减少有关，继发于AMPA受体增强。因此，在本研究中，使用植入后免疫金标记组织，在近端树突的CA 1放射层突触中寻找NMDAR GluN 1、GluN 2A和GluN 2B亚基可能减少的超微结构证据，这些组织来自从苯二氮卓类药物、泮（FZP）每日口服给药1周后停药2天的大鼠。GluN 1-免疫金密度和免疫阳性突触的百分比显着下降，从FZP撤回大鼠的组织。GluN 2B亚基也有类似的减少，但在BZ撤除后，GluN 2B-免疫标记在突触后密度内的相对横向分布没有改变。与GluN 2B亚基相反，GluN 2A亚基抗体标记的突触百分比和该亚基的免疫金标记密度不变。与每个NMDAR亚基相关的免疫金颗粒的空间定位与主要的突触后定位一致。因此，这些数据提供了直接的证据，减少突触GluN 1/GluN 2B受体和保护的GluN 1/GluN 2A受体在CA 1层辐射区在BZ撤回。基于集体的研究结果，在这个苯二氮卓类戒断焦虑模型，我们提出了一个功能模型，说明在苯二氮卓类戒断过程中兴奋性突触谷氨酸受体群体的变化。
Benzodiazepine withdrawal-anxiety is associated with enhanced AMPA receptor (AMPAR)-mediated glutamatergic transmission in rat hippocampal CA1 synapses due to enhanced synaptic insertion and phosphorylation of GluA1 homomers. Interestingly, attenuation of withdrawal-anxiety is associated with a reduction in NMDA receptor (NMDAR)-mediated currents and subunit expression, secondary to AMPA receptor potentiation. Therefore, in this study ultrastructural evidence for possible reductions in NMDAR GluN1, GluN2A and GluN2B subunits was sought at CA1 stratum radiatum synapses in proximal dendrites using postembedding immunogold labeling of tissues from rats withdrawn for 2-days from 1-week daily oral administration of the benzodiazepine, flurazepam (FZP). GluN1-immunogold density and the percentage of immunopositive synapses were significantly decreased in tissues from FZP-withdrawn rats. Similar decreases were observed for GluN2B subunits, however the relative lateral distribution of GluN2B-immunolabeling within the postsynaptic density did not change after BZ withdrawal. In contrast to the GluN2B subunit, the percentage of synapses labeled with the GluN2A subunit antibody and the density of immunogold labeling for this subunit was unchanged. The spatial localization of immunogold particles asssociated with each NMDAR subunit was consistent with a predominantly postsynaptic localization. The data therefore provide direct evidence for reduced synaptic GluN1/GluN2B receptors and preservation of GluN1/GluN2A receptors in the CA1 stratum radiatum region during BZ withdrawal. Based on collective findings in this benzodiazepine withdrawal-anxiety model, we propose a functional model illustrating the changes in glutamate receptor populations at excitatory synapses during benzodiazepine withdrawal.
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影响因子：
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作者：
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通讯作者：
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