Objective:To investigate the regulatory effects of TWIK-related K+ channel(TREK-1) blocker SID1900 on synaptogenesis in hippocampus in order to explore the anti-depression mechanism. Methods:Adult male C57BL/6J mice of 8 to 10 weeks were chosen to set up chronic mild unpredictable stress-induced anhedonia model of depression, and TREK-1 blocker of Spadin and SID1900 was injected for 28 days, and antidepressant response of TREK-1 blocker was evaluated on chronic unpredictable mild stress model by sucrose preference test, tail suspension test, force swimming test, open field test. On dosing 0, 7, 14, 21, 28 days. We extracted the post-synaptic density protein of PSD95 and synapsin1 in hippocampus on days of 28, then detected protein level of two markers synaptogenesis protein with Western blotting. Results:The chronic mild unpredictable stress significantly decreased the sucrose preference of model mice, and the time of immobility in FST was significantly increased compared with the control mice,the CUMS mice expressed specific endophenotype of depression. Chronic treatement with Spadin or SID1900 significantly increased the sucrose preference at the end of three-week treatment compared with the CUMS mice, but still decreased compared with the control mice, and the chronic three-week treatment did no affect force swimming test and Open-field test. Chronic treatement with Spadin or SID1900 significantly increased the sucrose preference at the end of four-week treatment compared with the CUMS mice, but there was no difference compared with the control mice. The immobility time in force swimming test and tail suspension test significantly decreased compare with the CUMS mice. Chronic treatement with Spadin or SID1900 for four weeks also increased protein level of two markers of synaptogenesis, the PSD95 and synapsin1 in the hippocampus. Conclusion:TREK-1 blocker (SID1900) can improve depressive symptoms and increase the expressions of synapse associated proteins PSD95 and Synapsin 1, which maybe the antidepression mechanism of TREK-1 blocker.
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