The Role of the Two‐Pore Domain Potassium Channel TREK ‐1 in the Therapeutic Effects of Escitalopram in a Rat Model of Poststroke Depression

摘要

Summary Aim 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. Methods 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. Results 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. Conclusion 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 .