| 1.BackgroundWith the essential symptoms of fear,anxiety,post-traumatic stress disorder(PTSD)has been regarded as a serious threat for human health.The onset of PTSD can be attributed to the combination of genes,environment,and social factors.In Traditional Chinese Medicine(TCM),the kidneys,the prenatal root of life,governs the emotion of fear and reproduction and growth.The physiological and pathological content related to the kidneys serves as the link to understand PTSD from the perspective of TCM.Thanks to the unique characteristics in clinical practice,in which body and mind are equally considered and treatment is determined based pattern deification and the mode of Biology-Psychology-Society(BPS)is focused,TCM presents significant advantages in caring and treating PTSD.Epigenetics links the clinical manifestation,behavior genetics,and neurobiology changes of PTSD.Epigenetics also explains well the connection of kidneys' disorders and PTSD.2.ObjectivesThis study was aimed to test the fetus injury due to maternal PTSD and examine the corrective effect from emotion simulation and Jin Kui Shen Qi Wan(JKSQW)?Behavior genetic and molecular methods were utilized and combined to screen the possible genes which could be modified by dis-regulation of methylation.Thus the genetic and epigenetic mechanism underlying the fetus injury owing to maternal PTSD and treatment by TCM approaches.3.MethodsSeventy-two pregnant SD rats were randomized into 5 groups,including control(n=12),emotion group(E,n=18),JKSQW group(J,n=12),combination of emotion and herb(CEJ,n=18),whose initial weight showed no statistic differences(p>0.05).Tests including OFT(open-filed test),SCT(sucrose consumption test),TOT(turn-over test),EOEO(ears opening and eyes opening)were employed to examine the behaviors genetics.Blood sample was taken from the offspring at 30 days after birth to perform the gene expression profiling and MeDIP-seq(methylated DNA immunoprecipitation sequencing).4.Results4.1 Behavior TestsThe OFT resulted in that the P offspring performed the lowest scores(p<0.05)and the E offspring the highest(p<0.05)among the five groups.The SCT resulted in that the P offspring consumed less sugar water than other four groups(p's<0.05)and there was no difference among the control,E,J,and CEJ(p's>0.05).The TOT result showed that the expect of PTSD was significantly smaller than that of other groups(p's<0.05)and a decline pattern of CHJ>E>J>control>P.The EOEO results showed that in both eyes-opening and ears-opening observation,the expects of PTSD were significantly smaller than that of other groups(p's<0.05)and a decline pattern of CHJ>E>J>control>P(p<0.05).4.2 Gene Expression ProfilingIn the comparison between P and control,112 significantly expressed gene(p's<0.05)were screened,among which 70 were up-regulated and 42 down-regulated.Five KEGG pathways were significantly annotated including endocytosis,MAPK signaling pathway,bile secretion,hypertrophic cardiomyopathy,and antigen processing and presentation.The emotion simulation normalized 31 of the down-regulated and 66 of the up-regulated genes in above 112 genes.JKSQW normalized 21 of the down-regulated and 32 of the up-regulated genes in above 112 genes.The combination of emotion and JKSQW normalized 25 of the down-regulated and 32 of the up-regulated genes in above 112 genes.Among the normalized genes,24 were found co-existed in E,J,and CEJ,involving the KEGG annotation of MAPK signaling pathway(Ntf3 and Pla2g5).4.3 MeDIP-seqIn the comparison between P vs control,943 genes were found up-methylated and 1775 down-methylated(p's<0.05).With the combining analyzing of the deferentially methylated and above expressed genes,11 were found co-existed and negatively related(R=-0.617,p=0.043).Ttr,Tsg101,Itgb6,Rtn4rl1,Sostdc1,Epn3 were up-regulated due to down-methylated while Cd300a,Wdfy3,Myh2,Ntf3 and F5 down-regulated due to up-methylated.In the comparison between E vs P,869 genes were found up-methylated and 1390 down-methylated(p's<0.05),which were compared with above 97 normalized genes.Rtn4rll,Hmhal and Wdfy3 were screened to be co-existed.In the comparison between J vs P,891 genes were found up-methylated and 730 down-methylated(p's<0.05),which were compared with above 53 normalized genes.Only Ntf3 were screened to be co-existed.In the comparison between CEJ vs P,1631 genes were found up-methylated and 1558 down-methylated(p's<0.05),which were compared with above 86 normalized genes.Itgb6,Epn3,Hmhal and Ntf3 were screened to be co-existed.5.Conclusion?.The negative impacts from maternal PTSD during pregnancy could handed down to the offspring,leading to malfunctioning in behavior tests,which could be recovered by the mimic emotional intervention and JKSQW feeding.?.The PTSD fetus injuries could cause disorder of the gene expression on the offspring.Emotion and JKSQW treatment could extensively normalize the dysregulation.MAPK signaling KEGG pathway including Ntf3 and Pla2g5 might play a key role of the treatment.?.Methylation modification could have been involved in the dys-regulation of gene expression profiling. |
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