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对氯苯丙氨酸增加大鼠杏仁核中谷氨酸受体1的转录。

P-chlorophenylalanine increases glutamate receptor 1 transcription in rat amygdala.

作者信息

Tran Lee, Keele N Bradley

机构信息

Institute for Biomedical Studies, Baylor University, Waco, Texas, USA.

出版信息

Neuroreport. 2011 Oct 26;22(15):758-61. doi: 10.1097/WNR.0b013e32834ae2a1.

Abstract

The amygdala is a key limbic structure strongly implicated in both epilepsy and anxiety disorders. Epilepsy-like mechanisms involve an increased glutamatergic activity, whereas disturbances in serotonin [5-hydroxytryptamine (5-HT)] systems are associated with anxiety-like behavior. Previous studies suggest that low 5-HT increases amygdala excitability, but the molecular mechanisms are not well characterized. Herein we explore the ability of low serotonin to increase glutamate receptor transcription. Using quantitative reverse transcriptase-polymerase chain reaction, we found that rats treated with P-chlorophenylalanine, an inhibitor of tyrosine-5-hydroxylase, resulted in a 21-fold increase in glutamate receptor 1 (GluR1) mRNA expression in the amygdala. These results suggest that low 5-HT induces hyperexcitability of amygdala neurons by increasing GluR1 transcription, and the upregulation of amygdala GluR1 may be important in the pathophysiology of anxiety disorders.

摘要

杏仁核是一个关键的边缘系统结构,与癫痫和焦虑症都密切相关。癫痫样机制涉及谷氨酸能活性增加,而血清素[5-羟色胺(5-HT)]系统紊乱与焦虑样行为有关。先前的研究表明,低5-HT会增加杏仁核的兴奋性,但其分子机制尚未得到充分表征。在此,我们探讨了低血清素增加谷氨酸受体转录的能力。使用定量逆转录聚合酶链反应,我们发现用酪氨酸-5-羟化酶抑制剂对氯苯丙氨酸处理的大鼠,其杏仁核中谷氨酸受体1(GluR1)mRNA表达增加了21倍。这些结果表明,低5-HT通过增加GluR1转录诱导杏仁核神经元的过度兴奋,杏仁核GluR1的上调可能在焦虑症的病理生理学中起重要作用。

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