Study On The Mechanism Of The Antidepressant-like Effect Of Dexmedetomidine By Regulating The BDNF Signal In MPFC

Objective:To investigate the rapid antidepressant effect and potential mechanism of dexmedetomidine,so as to provide a theoretical basis for its antidepressant effect.Methods:In this study,healthy adult C57 male mice(6-8 weeks old,20-25g)were tested and given various chronic mild stimuli to construct a chronic unpredictable mild stress(CUMS)depression model.Then,the antidepressant efficacy was assessed.The depression-like behavior of animals was evaluated through sucrose water preference test,forced swimming test and open-field test,and moreover the effect of dexmedetomidine on short-term(24h)depression-like behavior in mice was observed.In this study,Western blot(WB)was used to detect the expression of brain-derived neurotrophic factor(BDNF),postsynaptic density protein 95(PSD95)and the 2B subunit of N-methyl-D-aspartic acid receptor(NR2B)in the medial prefrontal cortex(mPFC)of mice,so as to explore the antidepressant mechanism of dexmedetomidine.Meanwhile,an brain slice electrophysiological test was introduced to observe the effect of dexmedetomidine on electrical activity of cone neurone in mPFC.The action potential(AP)was used to reflect the excitatory activity function of neurone;and the spontaneous excitatory postsynaptic currents(sEPSC)were used to reflect the excitatory synaptic transmission function of cone neurone in the mPFC.Results:CUMS depression model was successfully established.In the depression model group,the sucrose water preference of mice decreased,the forced swimming immobility time increased significantly,and the animals showed the depression-like behavior.The test results showed that dexmedetomidine could reverse effects of chronic mild stimuli on mice,such as decreased the preference of sucrose water and increased the forced swimming immobility time,and exerted its rapid antidepressant-like effect.In open-field test,dexmedetomidine had no obvious effect on the movement ability of mice.The results of WB found that dexmedetomidine could reverse the decreased expression of BDNF,PSD95 and NR2B in the mPFC of CUMS model mice.Brain slice electrophysiological test showed that dexmedetomidine could increase the generation frequency of action potential of cone neurone in the mPFC,as well as the activity of cone neurone,and could exert its rapid antidepressant effect by increasing the excitatory presynaptic transmission function of cone neurone in the mPFC.Conclusion:Dexmedetomidine might promote the expression of BDNF,PSD95 and NR2B in the mPFC,activate the the intracellular signaling pathway,reverse mPFC synaptic function transmission disorder caused by depression,and increase the excitability and excitatory presynaptic transmission function of cone neurone in the mPFC,thus play a rapid antidepressant-like effect.