CD44-mediated Early-stage Epileptogenesis

The epilepsiesarea family of neurological disorders is in common arising from groups of abnormal synchronized electrical activities of cerebral neurons.Through brain injuries evoluting to the occurrence of spontaneous recurrent seizures(SRS),this developing time window is called epileptogenesis.The mechanism under epileptogenesis in unknow,neither with efficient therapy during this period.Our purpose is using omics method to explore the mechanism under early-stage of epileptogenesis in PILO epilepsy model,and finding the effective therapy strategy to intervene the epileptogenesis.In order to exploring the mechanism under early-stage of epileptogenesis and finding the effective therapy strategy to intervene the SRS,we applying the hippocampus samples of pilocarpineepilepsy model to RNA-sequencing,finding that there are numerous inflammatory related genes changed significantly in PILO group compared to control group.After supplying IPA analyzing software,the research focused on highly related genes and pathway to continueing mRNA and protein levels confirming.Finaly solid data confirm the two genes,CD44 and SERPINE1,up-regulated significantly during early-stage of epileptogenesis in both transcriptional and translational levels.Additonally,via analysis souftware and papers,it is an interesting discovery that these genes are both involved in TGF-?pathway but located in different rank.CD44 is the up-regulator and PAI-1,the protein ecoded by SERPINE1 gene,is the downstream effector in TGF-?pathway.Therefore trying to inhibit the expression of CD44,we are going to explore the expression of PAI-1 protein and the levels of SRS and apoptosis,then confirming the effect of CD44 and PAI-1 during early-stage of epileptogenesis,to find out the therapy strategy targeting epileptogenesis by mechnism.Meanwhile,based on the previous data,we explore the mechanism under.We explored the apootosis related actylated p53 and ite deactylated enzyme–SIRT1,then got to know that NAD~+intervention to early-stage of epileptogenesis in PILO epilepsy model hippocampus tissue,significantly restore the PILO induced Acp53 high level but have no obvious change on PILO induced SIRT1 depletion.This demonstrated that NAD~+intervention might involve the p53 correlaetd apoptosis pathway,but do not through the function of SIRT1 on deacylation.The further reaeach will continue to understand this mechanism in detail.Furthermore,we also applied microRNA-seq to make it clear that the changing condition in microRNA level during early-stage of epileptogenesis,to investigate the reaction under post-transcriptional interaction between mRNA and microRNA,then find out the efficient biomarker and therapy to epilepsy.