Effects Of Icariin On Depression-like Behaviors And Expressions Of ?mGluRs And EAAT2 In The Brain In Prenatal Stress Offspring

Objective:To observe the effects of icariin on depression-like behaviors induced by prenatal stress(PS),I metabotropic glutamate receptors(mGluRl,mGluR5)and transporter(EAAT2)expressions in hippocampus and prefrontal cortex were determined,and further explore antidepressant effect of icariin.Methods:1.The model of depression was established by using chronic restraint stress.Sprague-Dawley(SD)rats were randomly divided into five groups:Control group(CON),prenatal stress group(PS),saline group(NS),icariin-H group(ICA-80mg/kg)and icariin-L group(ICA-40mg/kg).Icariin was administered by intragastric administration.2.The depression-like behaviors in each group were evaluated by Sucrose Preference Test,Forced Swimming Test and Open-Field Test.3.The protein expressions of mGluRl,mGluR5 and EAAT2 in hippocampus and prefrontal cortex were detected by Western Blot(WB).4.mGluR1,mGluR5 and EAAT2 mRNA expressions in hippocampus and prefrontal cortex were detected by Real-Time quantitative PCR(RT-PCR).Results:1.Sucrose Preference Test results showed that there was no statistical difference in total intake between groups.The sucrose preference percentage in PS group significantly decreased compared with CON.Long-time treatment with icariin(80mg/kg or 40mg/kg)could significantly increase sucrose preference percentage compared to NS group.2.The results of Forced Swimming Test showed a significant increase in the total immobility time and a significant decrease in struggling time in PS group compared to CON.Icariin(80mg/kg or 40mg/kg)could obviously shorten the total immobility time and increase the struggling time.3.In Open-Field Test,the time spent in central area,center crossing numbers and rearing numbers were decreased in PS group compared to CON.Long-time treatment of icariin(80mg/kg or 40mg/kg)could significantly increase the time spent in central area and center crossing numbers,but there was no significant difference in rearing numbers between icariin treatments and NS group.There was no significantly statistical difference in the numbers of grooming between groups.4.Western blot results showed that PS induced the protein expressions of mGluRl and mGluR5 markedly increased and EAAT2 protein expressions decreased in hippocampus and prefrontal cortex compared with CON.Treatment with icariin(80mg/kg),the protein levels of mGluR5 in hippocampus and prefrontal cortex significantly decreased,the EAAT2 levels in hippocampus obviously increased and mGluR1 levels in prefrontal cortex significantly decreased compared to NS group.Moreover,treatment with icariin(40mg/kg),mGluRl levels markedly decreased and EAAT2 levels significantly increased in hippocampus and prefrontal cortex,mGluR5 protein levels in hippocampus significantly reduced compared with NS group.5.RT-PCR results showed that PS induced an increase in mGluRl and mGluR5 mRNA levels and a significant decrease in EAAT2 mRNA levels in hippocampus and prefrontal cortex compared to CON.Treatment with icariin(80mg/kg or 40mg/kg),the expressions of mGluR1,mGluR5 and EAAT2 mRNA in the hippocampus and prefrontal cortex were significantly reversed in prenatal stressed offspring.Conclusion:1.PS induced depression-like behaviors in male offspring rats,while icariin could improve depression-like behaviors in prenatal stress offspring.2.PS induced mGluRs expressions increased and EAAT2 expressions decreased in the hippocampus and prefrontal cortex,and Icariin reversed the expressions of mGluRs and EAAT2 in the two brain regions and alleviated the depressive behaviors.