Hydrogen Sulfide Attenuates β₂-microglobulin-induced Cognitive Dysfunction Of Rats Involving Recovery Of Hippocampal Autophagic Flux

[Background and Objective]β2-microglobulin(B2M)is a systemic pro-aging factor and accumulation of B2 M impairs cognitive function.Hydrogen sulfide(H2S),as a neuroprotective gas signaling molecule,plays a important role in regulating cognitive function.Autophagy is an important self-protective mechanism in cells and plays a important role in cognitive function.Therefore,the present work was to explore whether H2 S attenuates the B2M-induced cognitive dysfunction and to investigate whether its underlying mechanism involves regulating the level of autophagy in the hippocampus.[Methods]1.Adult male SD rats were injected with B2M(0.3 μg,i.c.v.,single dose)into the lateral ventricle to establish a cognitive impairment model.2.The cognitive functions of rats were detected by Y-maze test,novel object recognition(NOR)test,and Morris water maze(MWM)test.3.The number of hippocampal autophagosome and autolysosome were observed by transmission electron microscopy.4.The expression of p62 protein in hippocampus was detected by Western Blot.[Results]1.H2S attenuates B2M-induced cognitive dysfunction in ratsAfter pretreated with Na HS(30 and 100 μmol/kg/d,i.p.)for 7 d,rats were cotreated with B2M(0.3 μg,i.c.v.,single dose)for one day and Na HS(30 and 100 μmol/kg/d,i.p.)for 6 d.The cognitive functions of rats were tested by the Y-maze test,the NOR test and the MWM test.We found that Na HS increased the alternation performance in the Y-maze test and the discrimination index in NOR test of B2M-exposed rats,respectively.Furthermore,In the MWM test,Na HS significantly shortened the escape latency in the 4th and 5th d in the acquisition phase and increased the crossing times as well as spending time in the target quadrant in the probe trial of B2M-exposed rats.Taken together,H2 S improves B2M-elicited cognitive impairment.2.H2 S reverses the blocking effect of B2 M on autophagic flux in the hippocampus of ratsIn order to explore whether H2 S affects autophagic flux in hippocampus of B2M-exposed rats,we observed the number of autophagosomes and the expression of p62 in the hippocampus of rats.Compared with the control group,B2 M significantly increased the ratio of autophagosome to autolysosome and the expression of p62 protein in the hippocampus of rats.After treatment with Na HS,the ratio of autophagosome to autolysosome and the expression of p62 protein were significantly decreased in the hippocampus of B2M-exposed rats.Taken together,H2 S recovers the hippocampal autophagic flux in B2M-exposed rats.[Conclusion]Hydrogen sulfide attenuates B2M-induced cognitive dysfunction,involving recovery of autophagic flux in the hippocampus of rats.