Effects Of Crocin On Learning And Memory And Expression Of BDNF And CREB In Hippocampus Of Autism Model Rats

Objective: To explore the effects of crocin on learning and memory,the number of hippocampal neurons,the expression of brain-derived neurotrophic factor(BDNF)and cyclic AMP response element binding protein(CREB)in autism model rats.So as to provide a new idea and direction for crocin in treatment of autism.Methods: Twenty healthy and clean female Wistar rats were randomly selected and intraperitoneally injected with sodium valproate on E12.5 day according to Schneider’s method,VPA(600 mg / kg)was labeled as pregnant mice in VPA group,and their offspring were in autism model group;10 pregnant mice were randomly selected and intraperitoneally injected with the same dose of normal saline,labeled as pregnant mice in NS group,and their offspring were in normal control group.Methods: 80 7-day-old rats in autism model group and 40 7-dayold rats in normal control group(NS group)were randomly selected.The rats in autism model group were randomly divided into two groups,namely,40 rats in crocin group(CVPA group)and 40 rats in solvent control group(VPA group).P7,P14 and p21 time windows in CVPA group were selected and labeled as cvpa-1 group,cvpa-2 group and cvpa-3 group,and crocin 50 mg / K was injected intraperitoneally every day g.The duration was 21 days;the same time window was selected for vpa-1 group,vpa-2 group,vpa-3 group,NS-1 group,NS-2 group and ns-3 group in VPA group and NS group,and the same dose of normal saline was injected intraperitoneally every day for 21 days.The behavior and learning and memory ability of offspring rats were observed at different intervention time windows.Nissl staining,immunofluorescence,Western blotting and image analysis were used to observe the changes of hippocampal neuron morphology,Neu N positive cell number and protein expression of BDNF and CREB in neonatal rats at different intervention time windows.Results:(1)Compared with NS group,VPA group had less weight gain and fewer offspring(P < 0.05).(2)Compared with NS group,VPA group had significantly lower body weight in P7,P21,P28,P35,P42;P28,VPA group had more stereotyped repetitive actions and less social communication;P28,P35,P42,VPA group had more brain weight and lower learning and memory ability.Compared with NS-1 group,the number of Neu N positive cells in hippocampus of VPA-1 group increased in P7 time window(P < 0.05),and the expression of BDNF and CREB protein increased(P < 0.05);compared with NS-2 group and NS-3 group,the number of Neu N positive cells in hippocampus of VPA-2 group and VPA-3 group decreased in P14 and P28 time window(P < 0.05),The expression of BDNF and CREB protein decreased(P< 0.05)(3)After intervention with crocin,compared with VPA group,the weight of offspring in CVPA group increased(P < 0.05),but there was no difference in brain weight(P > 0.05);when the intervention time window of crocin was P7 and P14,the learning and memory ability of offspring in CVPA-1 group and CVPA-2 group increased(P < 0.05),and the number of Neu N positive cells in hippocampus increased compared with VPA-1 group and VPA-2 group,respectively Compared with VPA-3 group,CVPA-3 group had no significant difference in learning and memory ability,Neu N positive cells in hippocampus,BDNF and CREB protein(P > 0.05).Conclusion: Crocin intervention can improve the learning and memory ability of autism model rats,increase the number of Neu N positive cells in hippocampus,promote the expression of BDNF and CREB protein in hippocampus of autism model rats;crocin intervention has different effects on autism model rats due to different medication time windows,P7 and P14 intervention time windows have improvement effect,21 intervention time window has no obvious effect.