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

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.

• Authors: Dai-Hua Lin, Xiang-Rong Zhang, Dong-Qing Ye, Guang-Jun Xi, Jiao-Jie Hui, Shan-Shan Liu, Lin-Jiang Li, Zhi-Jun Zhang
• Journal: CNS neuroscience & therapeutics (CNS Neurosci Ther) Vol. 21 Issue 6 Pg. 504-12 (Jun 2015) ISSN: 1755-5949 [Electronic] England
• PMID: 25675906 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons Ltd.

Chemical References

• Potassium Channels, Tandem Pore Domain
• Serotonin Uptake Inhibitors
• potassium channel protein TREK-1
• Citalopram

Topics

• Animals
• Body Weight (drug effects)
• Brain (drug effects, metabolism)
• Cell Proliferation (drug effects, genetics)
• Citalopram (therapeutic use)
• Depression (drug therapy, etiology, pathology)
• Disease Models, Animal
• Exploratory Behavior (drug effects)
• Food Preferences (drug effects)
• Gene Expression Regulation (drug effects)
• HEK293 Cells
• Humans
• Male
• Membrane Potentials (drug effects, genetics)
• Patch-Clamp Techniques
• Potassium Channels, Tandem Pore Domain (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Selective Serotonin Reuptake Inhibitors (therapeutic use)
• Stroke (complications)