Glial glutamate transporter and glutamine synthetase regulate GABAergic synaptic strength in the spinal dorsal horn.
Glial glutamate transporter and glutamine synthetase regulate GABAergic synaptic strength in the spinal dorsal horn.
复制标题
DOI：
10.1111/j.1471-4159.2012.07694.x
复制
发表时间：
2012-05
影响因子：
4.7
通讯作者：
Weng HR
中科院分区：
文献类型：
--
作者：
Jiang E;Yan X;Weng HR
脊髓背角中GABA能突触强度降低（“去抑制”）是促成病理性疼痛发展和维持的关键机制。然而，导致脊髓背角抑制解除的机制仍然难以捉摸。我们研究了胶质谷氨酸转运体（GLT-1和GLAST）和谷氨酰胺合成酶在维持脊髓背角GABA能突触活动中的作用。在大鼠脊髓背角浅层神经元记录到GABA能抑制性突触后电流（eIPSC）、自发性IPSC（sIPSC）和微型IPSC（mIPSC）。我们使用（2S，3S）-3-[3-[4-（三氟甲基）苯甲酰氨基]苄氧基]天冬氨酸（TFB-TBOA）阻断GLT-1和GLAST，使用二氢红藻氨酸（DHK）仅阻断GLT-1。我们发现，在脊髓背角中阻断GLAST和GLT-1以及仅阻断GLT-1降低了GABA能eIPSC的振幅，以及GABA能sIPSC或mIPSC的振幅和频率。药理学抑制胶质谷氨酰胺合成酶对GABA能eIPSC和sIPSC具有相似的作用。我们提供的证据表明，神经胶质谷氨酸转运蛋白抑制诱导的GABA能强度降低是由于星形胶质细胞和神经元之间的谷氨酸-谷氨酰胺循环导致GABA合成不足。因此，我们的研究结果表明，缺乏胶质细胞谷氨酸转运蛋白和谷氨酰胺合成酶显着减弱GABA能突触的强度在脊髓背角，这可能是一个重要的突触机制，神经胶质细胞的相互作用引起的功能障碍的星形胶质细胞在病理性疼痛条件。
Decreased GABAergic synaptic strength (“disinhibition”) in the spinal dorsal horn is a crucial mechanism contributing to the development and maintenance of pathological pain. However, mechanisms leading to disinhibition in the spinal dorsal horn remain elusive. We investigated the role of glial glutamate transporters (GLT-1 and GLAST) and glutamine synthetase in maintaining GABAergic synaptic activity in the spinal dorsal horn. Electrically evoked GABAergic inhibitory postsynaptic currents (eIPSCs), spontaneous IPSCs (sIPSCs) and miniature IPSCs (mIPSCs) were recorded in superficial spinal dorsal horn neurons of spinal slices from young adult rats. We used (2S, 3S)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (TFB-TBOA), to block both GLT-1 and GLAST and dihydrokainic acid (DHK) to block only GLT-1. We found that blockade of both GLAST and GLT-1 and blockade of only GLT-1 in the spinal dorsal horn decreased the amplitude of GABAergic eIPSCs, as well as both the amplitude and frequency of GABAergic sIPSCs or mIPSCs. Pharmacological inhibition of glial glutamine synthetase had similar effects on both GABAergic eIPSCs and sIPSCs. We provided evidence demonstrating that the reduction in GABAergic strength induced by the inhibition of glial glutamate transporters is due to insufficient GABA synthesis through the glutamate-glutamine cycle between astrocytes and neurons. Thus, our results indicate that deficient glial glutamate transporters and glutamine synthetase significantly attenuate GABAergic synaptic strength in the spinal dorsal horn, which may be a crucial synaptic mechanism underlying glial-neuronal interactions caused by dysfunctional astrocytes in pathological pain conditions.
登录
查看更多内容
影响因子：
25
作者：
Fredj, Naila Ben;Burrone, Juan
通讯作者：
Burrone, Juan
影响因子：
2.5
作者：
Ingram, Rachel A.;Fitzgerald, Maria;Baccei, Mark L.
通讯作者：
Baccei, Mark L.
DOI：
10.1523/jneurosci.0032-11.2011
发表时间：
2011-05-04
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Hunt RF;Scheff SW;Smith BN
通讯作者：
Smith BN
影响因子：
25
作者：
Balakrishnan, Veeramuthu;Kuo, Sidney P.;Roberts, Patrick D.;Trussell, Laurence O.
通讯作者：
Trussell, Laurence O.
影响因子：
7.4
作者：
Liaw, WJ;Stephens, RL;Tao, YX
通讯作者：
Tao, YX