Hydrogen Sulfide Improves Synaptic Plasticity In Streptozotocin-induced Diabetic Rats:Involving In Hippocampal Metabolism Reprogramming

[Background and Objective] Our previous study has found that H2 S improved cognitive function in STZ-induced diabetic rats.However,the underlying mechanism remained unknown.Hippocampal synaptic plasticity plays an important role in cognitive formation.Thus,we explored whether H2 S ameliorates impaired synaptic plasticity in STZ-exposed rats.Warburg effect and oxidative phosphorylation are two classical metabolic statuses in the hippocampus.Recent findings clearly showed that the Warburg effect plays a key mediated role in synaptic plasticity.Thus,we explored whether H2 S improved impaired synaptic plasticity in STZ-exposed rats by metabolic reprogramming between aerobic glycolysis and oxidative phosphorylation to treat DACD.[Method] Male Sprague Dawley(SD)rats were given intraperitoneal injection with sterptozotocin(STZ,55 mg/kg)for once.If the random blood glucose level of the rat was more than 16.7 mmol/L 3 days later,regarded it as made model successfully.Then the rats were treated with Na HS(30,100 ?mol/kg/d)for 30 days.Electron microscopy was used to observe the changes in synaptic microstructure.Western blotting was used to detect the expression of synapse related protein synapsin-1 and PSD-95;Warburg effect related proteins,such as HK-2,PKM-2,PDK-1,PDH,and LDHA;and oxidative phosphorylation related protein CI-CV.The contents of hippocampal lactate were detected by lactate assay kit II.[Result] 1.H2 S improved hippocampal synaptic plasticity in the STZ-exposed rats.1)H2S increased the hippocampal synaptic density in the STZ-exposed rats.The results of electron microscopy showed that the synaptic density in the hippocampal CA1 and CA3 regions of the STZ-exposed rats was significantly reduced compared to the control group;however,Na HS(100 ?mol/kg/d,30 d)significantly increased the synaptic density in the hippocampal CA1 and CA3 regions of STZ-exposed rats.2)H2S improved the synaptic interface structure in the hippocampal CA1 and CA3 regions of STZ-exposed rats.In the hippocampal CA1 and CA3 regions of STZ-exposed group,the length of synaptic active zone and the thickness of postsynaptic density were reduced as well as the structural parameter of synaptic gap width was increased.However,Na HS(100 ?mol/kg/d,30 d)significantly increased the length of synaptic active zone and the thickness of postsynaptic density as well as narrowed the synaptic gap width in the STZ-exposed rats.3)H2S increased the expressions of synapsin-1 and psd-95 in the hippocampus of STZ-exposed rats.The results of western blotting showed that the expressions level of synapsin-1 and PSD-95 were decreased in the hippocampus of STZ-exposed rats;however,Na HS(100 ?mol/kg/d,30 d)increased the expressions of synapsin-1 and PSD-95 in the hippocampus of STZ-exposed rats.2.H2 S up-regulated Warburg effect in STZ-exposed rats.1)H2S up-regulated the key enzyme of Warburg effect in the hippocampus of STZ-exposed rats.Western blotting showed that the expressions of HK-2,PKM-2,PDK-1,and LDHA were significantly decreased,while the expressions of PDH was significantly increased,in the hippocampus of STZ-exposed rats.However,Na HS(100 ?mol/kg/d,30 d)increased the expressions of HK-2,PKM-2,PDK-1,and LDHA,while decreased the expression of PDH,in the hippocampus of STZ-exposed rats.2)H2S increased the content of lactate in the hippocampus of STZ-exposed rats.The content of lactate in the hippocampus of STZ-exposed group was significantly decreased,while Na HS(100?mol/kg)increased the content of lactate in the hippocampus of STZ-exposed rats.3.H2 S down-regulated oxidative phosphorylation(Ox Phos)in the hippocampus of STZ-exposed rats.The results of western blotting showed that the expressions of mitochondrial respiratory complexes chain associated protein C-I,C-II,C-III,C-IV,C-V obviously were increased in the hippocampus of STZ-exposed rats,while Na HS(100 ?mol/kg)decreased the expressions of C-I,C-II,C-III,C-IV,C-V in the hippocampus of STZ-exposed rats.These results indicated that H2 S down-regulated Ox Phos in the hippocampus of STZ-exposed rats.[Conclusion] H2 S improves hippocampal synaptic plasticity in the STZ-exposed rats,which involves in the hippocampal glucose metabolism reprogramming.