?₂-microglobulin Induces Depressive-and Anxiety-like Behaviors In Rat And The Antagonistic Effects Of Hydrogen Sulfide

[Background and Objective]?₂-microglobulin?B2M?is an important neuroimmune protein and overactivation of B2 M impairs hippocampal neurogenesis.The impaired hippocampal neurogenesis and reduction of synaptic plasticity play crucial roles in the pathogenesis of depression and anxiety.Therefore,whether B2 M leads to depressive-and anxiety-like behaviors in rats?Hydrogen sulfide?H₂S?is a novel endogenous neurotransmitter.The previous studies in our laboratory found that H₂S has improving effect on depressive-and anxiety-like behaviors induced by diabetic rats,acute stress and chronic stress via attenuating hippocampal neuron damage and regulating synaptic plasticity.Therefore,we further investigated whether H₂S antagonizes B2M-induced depressive-and anxiety-like behaviors in rats.[Methods]Novelty-suppressed bean test?NSFT?,tail suspension test?TST?and forced swimming test?FST?were used to detect depressive-like behaviors of Sprague-Dawley?SD?male rats.Elevated plus-maze test?EPMT?was used to detect anxiety-like behaviors and open field test?OFT?was used to evaluate the spontaneous activity of SD rats.[Results]1.B2 M induces depressive-and anxiety-like behaviors in rats Compared with control group,the latency to feed in the NSFT was increased?the food consumption in 30 min was no significant difference between groups?,the immobility times in the TST and the FST were increased in the rats that were administered with exogenous B2M?0.3?g,i.c.v.,single dose?.There was no significant difference in total distance of rats in the open field test.The above results indicated that B2M induces depressive-like behaviors.In addition,B2M-treated rats displayed obvious decline in the number of entries into and the time spent in the open arm,while the number of total arm entries was no change in the EMPT,which indicated that B2 M exerts anxiety-like behaviors.2.H₂S antagonizes B2M-induced depressive-and anxiety-like behaviors in rats Sodium hydrosulfide?NaHS,30 and 100?mol/kg/d,i.p.,2 w?,a H₂S donor,significantly shorted the latency to feed in the NSFT?the food intake in 30 min is no difference among groups?and the immobility time in the TST in the B2M-exposed rats.Meanwhile,in the FST,NaHS?30and 100?mol/kg/d,i.p.,2 w?significantly decreased the duration of immobility in the B2M-exposed rats.There was no significant difference in the total distance of rats in the open field test.These results demonstrated that H₂S ameliorates B2M-triggered depressive-like behaviors.In the EPMT,Na HS?100?mol/kg/d,i.p.,2 w?markedly increased the number of entries into and the time spent in the open arm of B2M-exposed rats,while the number of total arm entries among groups was no change,which indicated that H₂S alleviates B2M-elicited anxiety-like behaviors.[Conclusion]1.B2 M induces depressive-and anxiety-like behaviors in rats;2.H₂S antagonizes B2M-induced depressive-and anxiety-like behaviors.