Effect of 7,8-dihydroxyflavone on autism-like behavior induced by sevoflurane exposure in neonatal mice
Objective:To explore the effect of 7,8-dihydroxyflavone(7,8-DHF)on autism-like behavior in mice induced by repeated exposure to sevoflurane in the early development stage.Methods:Seventy-four 7-day-old SPF C57BL/6 mice were randomly divided into the control group(Con group),sevoflu-rane group(Sev group),sevoflurane+vehicle group(vehicle group),and sevoflurane+7,8-DHF group(7,8-DHF group).At the age of 7 days,mice in the Sev group were exposed to air with 3%sevo-flurane and 30%oxygen for 2 hours per day for 3 consecutive days,while the mice in the Con group were only exposed to 30%oxygen.The mice in the 7,8-DHF group and vehicle group received the same exposure to sevoflurane as the Sev group,and they were intraperitoneally injected with 5 mg/kg of 7,8-DHF or equivalent volume of solvent once a day for 21 days after 3 weeks.Social behavioral tests and sampling of mice(dorsal hippocampal tissue)were performed at the age of 7 weeks.Results:Compared with the Con group,the mice in the Sev group showed a deficiency of social novelty preference,longer self-grooming time,and decreased expression of brain-derived neurotrophic factor(BDNF)protein and mRNA in dorsal hippocampal tissue.Compared with the vehicle group,the social novelty preference defect and mechanical repetitive behavior of the mice in the 7,8-DHF group were im-proved.Conclusion:Repeated exposure to sevoflurane in the early development stage of the mice leads to autism-like behavior and reduces expression of BDNF in the dorsal hippocampus in adulthood.How-ever,7,8-DHF could effectively reverse the disorders caused by neonatal exposure to sevoflurane.