Lin Dai-Hua, Zhang Xiang-Rong, Ye Dong-Qing, Xi Guang-Jun, Hui Jiao-Jie, Liu Shan-Shan, Li Lin-Jiang, Zhang Zhi-Jun
Department of Neurology, Affiliated with ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, China.
Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, China.
CNS Neurosci Ther. 2015 Jun;21(6):504-12. doi: 10.1111/cns.12384. Epub 2015 Feb 10.
Poststroke depression (PSD) is one of the most common neuropsychiatric complications after stroke. TREK-1, a two-pore-domain potassium channel, has been implicated in the pathogenesis of stroke and depression. The aim of this study was to investigate whether TREK-1 plays a role in the therapeutic effects of the selective serotonin reuptake inhibitor (SSRI) escitalopram in a rat PSD model.
The whole-cell patch-clamp technique was performed to assess the effect of escitalopram on recombinant TREK-1 currents in HEK293 cells. The expression of TREK-1 mRNA and protein was measured in the hippocampus and prefrontal cortex (PFC), and neural stem cell (NSC) proliferation was detected in the hippocampal dentate gyrus (DG) in PSD rats after 3 weeks of escitalopram administration.
Escitalopram reversibly inhibited TREK-1 currents in a concentration-dependent manner. Chronic treatment with escitalopram significantly reversed the reductions in weight gain, locomotor activity, and sucrose preference in PSD rats. The expressions of TREK-1 mRNA and protein were significantly increased in hippocampal CA1, CA3, DG, and PFC in PSD rats, with the exception of TREK-1 mRNA in hippocampal CA1. NSC proliferation was significantly decreased in hippocampal DG of PSD rats. Escitalopram significantly reversed the regional increases of TREK-1 expression and the reduction of hippocampal NSC proliferation in PSD rats.
TREK-1 plays an important role in the therapeutic effects of the SSRI escitalopram in PSD model, making TREK-1 an attractive candidate molecule for further understanding the pathophysiology and treatment of PSD.
脑卒中后抑郁（PSD）是脑卒中后最常见的神经精神并发症之一。TREK-1是一种双孔域钾通道，与卒中和抑郁的发病机制有关。本研究旨在探讨TREK-1在选择性5-羟色胺再摄取抑制剂（SSRI）艾司西酞普兰对大鼠PSD模型治疗作用中是否发挥作用。
采用全细胞膜片钳技术评估艾司西酞普兰对HEK293细胞中重组TREK-1电流的影响。在给予艾司西酞普兰3周后，检测PSD大鼠海马和前额叶皮质（PFC）中TREK-1 mRNA和蛋白的表达，并检测海马齿状回（DG）中的神经干细胞（NSC）增殖情况。
艾司西酞普兰以浓度依赖性方式可逆性抑制TREK-1电流。艾司西酞普兰长期治疗可显著逆转PSD大鼠体重增加、运动活动和蔗糖偏好的降低。PSD大鼠海马CA1、CA3、DG和PFC中TREK-1 mRNA和蛋白的表达显著增加，但海马CA1中的TREK-1 mRNA除外。PSD大鼠海马DG中的NSC增殖显著减少。艾司西酞普兰可显著逆转PSD大鼠TREK-1表达的区域增加和海马NSC增殖的减少。
TREK-1在SSRI艾司西酞普兰对PSD模型的治疗作用中起重要作用，使TREK-1成为进一步了解PSD病理生理学和治疗方法的有吸引力的候选分子。
