孕期抑郁大鼠海马区circFBXW4下调与子代神经发育的相关性OA

Objective To investigate the alterations in hippocampal circFBXW4 expression within a rat model of perinatal depression,as well as its association with depression-related behaviors and the neurodevelopment of offspring.Methods Pregnant Sprague-Dawley(SD)rats were randomly allocated into a control group and an experimental group.The experimental group was exposed to chronic unpredictable mild stress(CUMS).The behavioral performances of maternal rats and their offspring were assessed using the sucrose preference test(SPT),open-field test(OFT),and elevated plus-maze(EPM).Serum corticosterone levels and circFBXW4 expression in the maternal brain tissue were determined.Hematoxylin-eosin(HE)staining was carried out on the hippocampal tissue of offspring on postnatal day 7.Moreover,Spearman correlation analysis was employed to evaluate the rela-tionship between circFBXW4 and behavioral indicators.Results When compared with the control group,maternal rats in the CUMS group exhibited a decreased sucrose preference index(U=104.00,P=0.049),a reduced central activity time(t=7.67,P<0.001)and distance(t=6.29,P<0.001)in the OFT,as well as a decreased open-arm time(U=122.00,P<0.001),distance(U=118.00,P=0.001),and entries(U=119.50,P<0.001)in the Elevated Plus-Maze(EPM).Serum corticosterone levels were elevated(t=-3.56,P=0.001),and the expression of hippocampal circFBXW4 was reduced(U=120.00,P=0.006),which showed a negative corre-lation with sucrose preference and OFT indicators.In the offspring,the CUMS group demonstrated a decreased sucrose preference index(U=181.00,P<0.001),a reduced central activity time(U=196.00,P<0.001)and distance(t=4.87,P<0.001)in the OFT,and a decreased open-arm time(U=196.00,P<0.001)and distance(U=196.00,P<0.001)in the EPM.The offspring's serum corticosterone levels were increased(t=-2.46,P=0.040).Conclusions circFBXW4 was significantly reduced in the perinatal depression model when compared to the control group,and this reduction was closely associated with maternal depression-like behaviors.Maternal depression had long-lasting effects on offspring,which were manifested as anhedonia,decreased exploratory behav-ior,and hippocampal structural abnormalities.These findings strongly suggest that circFBXW4 may be involved in perinatal depression and exert intergenerational effects,and it has potential as a molecular biomarker.