title: The Role of the Two-Pore Domain Potassium Channel TREK-1 in the Therapeutic Effects of Escitalopram in a Rat Model of Poststroke Depression.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Neurology, Affiliated with ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, China.
authors: Dai-Hua
authors: DH
authors: Lin
authors: Department of Neurology, Affiliated with ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, China.
authors: Xiang-Rong
authors: XR
authors: Zhang
authors: Department of Neurology, Affiliated with ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, China.
authors: Dong-Qing
authors: DQ
authors: Ye
authors: Department of Neurology, Affiliated with ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, China.
authors: Guang-Jun
authors: GJ
authors: Xi
authors: Department of Neurology, Affiliated with ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, China.
authors: Jiao-Jie
authors: JJ
authors: Hui
authors: Department of Neurology, Affiliated with ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, China.
authors: Shan-Shan
authors: SS
authors: Liu
authors: Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, China.
authors: Lin-Jiang
authors: LJ
authors: Li
authors: Department of Neurology, Affiliated with ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, China.
authors: Zhi-Jun
authors: ZJ
authors: Zhang
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D015283:Citalopram / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005518:Food Preferences / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D018408:Patch-Clamp Techniques; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D020521:Stroke / Q000150:complications
chemical_list: D015283:Citalopram; D024683:Potassium Channels, Tandem Pore Domain; D017367:Selective Serotonin Reuptake Inhibitors; C103742:potassium channel protein TREK-1
keywords: Escitalopram; Poststroke depression; TREK-1 (TWIK-related potassium channel, type 1); Therapeutic effects