Effect Of Glucocorticoid Receptor’s Function On Expression Of MAOA By GC-KLF11-MAOA Pathway

Objective:To explore the effect of glucocorticoid receptor(GR)’s function on expression of monoamine oxidase A(MAOA)by GC-KLF11-MAOA PathwayMethods:(1)Grouping and administration:Three-week-old SHR rats were randomly divided into 4 groups,Control group(CON group),Methylphenidate group(MPH group),Dexamethasone group(DEX group)and Mifepristone group(RU486group),7 rats in each group.The rats in MPH group were given Methylphenidate(4mg/kg.d),while those in DEX group and RU486 group were treated with Dexamethasone(0.5 mg/kg.d)and Mifepristone(54 mg/kg.d)respectively.And the rats in CON group were treated with sterile water.Drug administrations were daily conducted by gavage at 8:00AM for 14 days continuously.(2)Behavior test:Levels of spontaneous activity and degrees of attention deficit of rats were evaluated by open field test and LAT maze test.(3)GR expression level evaluation:Immunohistochemical technique and image analysis were used to assess the expression of GR in prefrontal cortex with mean optical density(MOD)as index.(4)Evaluation of KLF11,MAOA expression:The expression of KLF11 protein and MAOA protein was detected by immunocytochemistry technique and image analysis with mean optical density(MOD)as index.(5)Statistical analysis:One-Way ANOVAs analysis,independent samples t-test,Least Significant Difference(LSD)-t test and Pearson correlation analysis were conducted for statistical analysis.P value<0.05 was considered to be statistically significant.Result:(1)Behavior test:After MPH intervention,the number of rearing(24.11±7.28)and corner crossing(61.67±19.37)in LAT maze test were significantly decreased(33.44±7.32,87.78±20.63)(P<0.05),and the number of rearing(24.44±11.27)and line crossing(56.44±12.50)in open field test were significantly decreased as well(48.67±12.65,81.67±13.10)(P<0.05).After DEX administration,decreasing of rearing numbers were found both in LAT maze test and open field test(22.00±5.39,25.44±6.88)(P<0.05),while numbers of corner crossing were significantly decreased in LAT maze test(81.11±14.09,P<0.05).(2)GR expression:After drug administration,MOD of GR expression in MPH group(0.242±0.102)and in DEX group(0.230±0.001)were both higher when compared with CON group(0.158±0.044)(P<0.05),while difference of the two group were not statistically significant(P>0.05).(4)Correlational analyses:As analyzed by linear regression,rearing times(R=0.635,R~2=0.403,P<0.05)and corner crossing numbers(R=0.914,R~2=0.836,P<0.05)of SHR in LAT maze together with rearing times(R=0.897,R~2=0.805,P<0.05)and line crossing numbers(R=0.92,R~2=0.846,P<0.05)of SHR in open field test were all negatively correlated with GR expression levels.(5)Levels of KLF11,MAOA expression:Comparing to CON group,MOD of both KLF11(0.139±0.01)and MAOA(0.143±0.01)expression were higher(0.108±0.01,0.123±0.00)after GC intervention(P<0.05).MAOA(0.112±0.01)expression was lower after RU486 administration when compared with CON group.However,RU486 administration did not decrease KLF11(0.124±0.00)expression(P<0.05).MPH treatment did not showe effect to KLF11(0.112±0.01)and MAOA(0.123±0.00)expression(P>0.05).Conclusion:(1)Administration of GR agonists and MPH could alleviate the hyperactivity and inattention displayed by SHR.(2)MPH may alleviate ADHD like behavior of SHR by improving GR function in the prefrontal cortex.(3)GR agonists may affect monoamine transmitters’function and improve AHDH symptom of SHR via GC-KLF11-MAO pathway.