Effects Of Quercetin On Behavior And Intestinal Flora In VPA Autism Model Mice

Objective: To study the effect of quercetin on the behavior and intestinal flora of VPA autism model mice.Methods: Three female SD rats were randomly selected and intraperitoneally injected with sodium valproate(VPA)on day 12.5 of pregnancy.The offspring mice were marked as the model group.In addition,one female SD rats were randomly selected and intraperitoneally injected with the same amount of normal saline on day 12.5 of pregnancy.Twenty mice of P21-day-old model group were randomly selected and randomly divided into two groups: control group(VPA group)and quercetin group(QUR group).Ten normal developing offspring mice were randomly selected as the normal group(NS group).The mice in the QUR group were intragastrically administered with 30 mg/kg/d quercetin,and the mice in the NS group and the VPA group were intragastrically administered with the same dose of normal saline.The fecal samples of each group were collected at P21,P28 and P35 days of age and stored in liquid nitrogen at-80 °C.The 16 S r RNA gene sequencing technology was used to detect the intestinal flora and metabolic level of each group.After collecting the samples,the stereotyped behavior,social interaction ability and spatial memory ability of each group were detected.Results: 1.Developmental level and behavioral test results showed that the body weight of the model group was significantly lower than that of the normal group,and the directional tendency ability was decreased.The degree of repetitive stereotyped behavior increased,and the spatial memory ability,social and social novelty ability decreased.The above differences were statistically significant(P<0.05).After quercetin intervention to P28 and P35 days of age,compared with the VPA group,the cumulative time of stereotyped behavior in the QUR group was reduced,and the ability of spatial memory,social and social novelty was improved.The differences were statistically significant(P<0.05).2.The results of intestinal flora detection showed that there was no significant difference in Alpha diversity and Beta diversity between the VPA group and the normal group.There Compared with the normal group,the ratio of Firmicutes/Bacteroides(F/B)in the control group decreased,and the model group was mainly dominated by Bacteroides and other bacteria(P<0.05).After quercetin intervention,the ratio of F/B changed with the intervention time.The relative abundance of Campylobacter,Proteobacteria and Clostridium in autistic model mice decreased after quercetin intervention(P<0.05).3.According to the results of metabolic level,the model group had lower ability in different metabolic pathways such as butyric acid synthesis,taurine metabolism,base excision repair,γ-aminobutyric acid degradation and tricarboxylic acid cycle(P<0.05);after quercetin intervention,the metabolic capacity of autistic model mice in base excision repair,acetyl coenzyme A fermentation to produce butyric acid and pyruvate fermentation to produce butyric acid was improved(P<0.05).4.According to the results of correlation analysis between the difference of flora and behavior in each group,there was a significant positive correlation between the spatial memory ability of autistic model mice and Prevotellaceae＿UCG-001(P<0.01);there was a significant positive correlation between stereotypical behaviors such as grooming and Veillonella(P<0.01).There was a significant negative correlation between social interaction disorder test(TE-TS)and Turicibacter(P<0.01).There was a significant negative correlation between social novelty disorder test(TS1-TS2)and Lachnospiraceae＿NK4A136(P<0.01).In addition,after quercetin intervention,autism model mice reduced the flora such as Veillonella which was positively correlated with stereotyped behavior(P<0.05),and increased the relative abundance of Lachnospiraceae＿UCG-010 which was negatively correlated with social novelty disorder(P<0.05),significantly changed the flora related to stereotyped,social and social novelty behavior.From the correlation between social ability and intestinal flora,it was found that Alphaproteobacteria,Rhodospirillales,and Christensenellaceae may be potential floras to improve social and social novelty disorders in autistic model mice.Conclusion: 1.Quercetin can improve the stereotyped behavior,social interaction and social novelty disorder and spatial memory ability of autistic model mice,but the difference in intervention duration does not have a short-term effect on autistic behavior.2.The different durations of quercetin intervention can regulate the balance of intestinal flora and improve metabolic capacity,and the intervention effect increases with the increase of intervention time.3.Quercetin may improve behavioral impairment in autism model rats by improving the microenvironment of intestinal flora and metabolic capacity.