The Regulatory Effects Of TREK-1 Blocker SID1900 On Synaptogenesis Protein

OBJECTIVE Recent studies have confirmed the role of two-pore domain potassium channel TREK1 in the pathophysiology of depression,and has been antidepressive target.However,the antidepressive mechanism of TREK-1 mediated response is not clear.In the present study,we intend to investigate the regulatory effects of TREK1 blocker SID 1900 on synaptogenesis in hippocampus,designed to explore the antidepressive mechanism.METHOD We selected adult male C57BL/6J mice of 8 to 10 weeks to set up chronic mild unpredictable stress-induced anhedonia modle of depression,and injected TREK 1 blocker of Spadin and SID 1900 for 28 days,and evaluated TREK1 blocker antidepressant response on chronic unpredictable mild stress modle by sucrose preference test,tail suspension test,force swimming test,Open-field test.In dosing 0,7,14,21,28 days.we extracted the post-synaptic density protein of 95 kDalton(PSD-95)and synapsinl in hippocampus on days of 28,then detected protein level of two markers Synaptogenesis protein with western blotting.RESULT The chronic mild unpredictable stress significantly decrease the sucrose preference of modle mice,and the time of immobility in FST is significantly increased compared with control mice,the CUMS mice expressed specific endophenotypes of depression.Chronic treatement with Spadin or SID 1900 significantly increased the sucrose preference at the end of three weeks treatment compared with CUMS mics,but still decreased compared with control mice,and the chronic treatment for three weeks did no effect on force swimming test and Open-field test.Chronic treatement with Spadin or SID1900 significantly increased the sucrose preference at the end of four weeks treatment compared with CUMS mics,and there was no difference compared with control mice.The immobility time in force swimming test and tail suspension test significantly decreased compare with CUMS mice.Chronic treatement with Spadin or SID 1900 for four weeks also increased protein level of two markers of synaptogenesis,the PSD-95 and synapsinl in the hippocampus.CONCLUSION We argued for a new role of TREK1 blocker(SID 1900)in synaptogenesis as both PSD-95 and synapsinl protein levels were further enhanced in the hippocampus,this maybe the antidepressive mechanism of TREK 1 blocker.