Behaviors And Inibition Of BDNF In Hippocampus Induced By Chronic Stress

[Background and Objective]More efficacious antidepressant therapies are in urgent demand. Desppression isassociated with neuronal damage and altered neuronal and structural plasticity inhippocampus. Hydrogen sulfide （H₂S） is a new gasotransmitter. Recent evidence hasdemonstrated that H₂S has important roles in neuroprotection and regulation ofsynaptic plasticity. Therefore, this study will investigate whether H₂S producesantidepressant-like effects.More and more evidences indicate that brain derived neurotrophic factor （BDNF）mediates the action of antidepressants through promoting the survival andproliferation of neurons and regulating the neuronal and structural plasticity inhippocampus. Thus, we speculate that BDNF invovles in the antidepressant-likeeffects of H₂S.Therefore, in the current study, we used the chronic unpredictable mild stressmodel to investigate the effects of H₂S on depression and explore the underlyingmechanisms.【Methods】40adult male Sprague Dawley rats （200–220g） were randomly distributed to4groups: control, CUMS, low dose NaHS （1.68mg/kg） treatment, and high dose NaHS（5.6mg/kg） treatment. CUMS rats were exposed to one stress per day for2w, andthen received2w of NaHS or vehicle injections during which CUMS continued. Depression-like behaviors was evaluated by the sucrose preference test, theforced swim test （FST）, and the locomotor activity. The expression of cystathioninebeta-synthase （CBS） in hippocampus was detected by Western Blot. The generationof H₂S in hippocampus was determined by the N,N-dimethyl-p-phenylenediaminesulphate （NNDPD） method. The level of BDNF in hippocampus was detected byWestern Blot and ELISA.[Results]1. CUMS causes the depression-like behaviors and inhibition of endogenous H₂Sgeneration in hippocampus.CUMS induced the decrease in sucrose preference and locomotion activity, theincrease in the time of immobility in FST, and the suppression in CBS expression andH₂S generation in hippocampus, which indicated that inhibition of H₂S generation inhippocampus is associated with CUMS-induced depression-like behaviors.2. H₂S reversed CUMS-induced depression-like behaviors.Compared with CUMS group, the sucrose preference and location in NaHS （1.68,5.6mg/kg） treatment groups are increase （P<0.05） and the immobility times in forceswim test is decrease （P<0.01）. These results demonstrated that H₂S inhibitsCUMS-induced depression-like behaviors.3. H₂S reversed the inhibition of BDNF expression in hippocampus induced byCUMS.CUMS （4w） inhibited the expression of BDNF in hippocampus （P<0.01） and thiseffect of CUMS was reversed by treatment with NaHS （1.68and5.6mg/kg）（P <0.01）, which indicated that upregulation of BDNF invovles in the antidepressant-likeeffects of H₂S.[Conclusion]1. H₂S reverse CUMS-induced depression-like behaviors.2. Upregulation of BDNF invovles in the antidepressant-like effects of H₂S.