Comparative Transcriptome Sequencing Studies On The Mechanism Of Lithium Upregulation Of Circadian Clock Gene Per2 And The Function Of CK1 ε/δ Kinase

Bipolar disorder is a serious mental disease,there are two kinds of phenotype of this disease,I type:severe mania and depression;II type:mild manic and severe depression.At the onset of the disease,there are potential dangers to the patients themselves and the people around them.With the development of medical treatment,there are many drugs and treatments for bipolar disorder,but lithium is still an important drug in the treatment of bipolar disorder.In the decades since lithium was found to treat the disorder,the link between bipolar disorder and biological clock disorders,such as recurrent bipolar disorder and sleep disorders,has been widely studied.But what is the molecular mechanism between them?Understanding the molecular mechanisms of action and targeting research into targeted drugs to treat the disease has become more important.Therefore,the research started from one of the directions:lithium up-regulates the expression of the circadian clock gene per2 to complete the molecular mechanisms.In the early,our laboratory has confirmed that lithium could indirectly up-regulate per2 by down-regulating e4bp4.U20S(U20S-Promoter-per2)and NIH3T3(NIH3T3-Promoter-per2)were treated with lithium,and then the treated cells were sequenced by RNA-seq.The sequencing results were classified and integrated found that in the two groups of the transcriptome sequencing results per2 genes were up-regulated,and The analysis results are in line with expectations.In addition to the clock pathway,lithium may also regulate clock genes through 39 other signaling pathways.We have confirmed that the lithium can up-regulated the circadian gene per2,however,the transcription factors are also involved in regulation.Therefore,we chose the U20S to confirm whether or not.The U20S was treated with lithium and CHX then and then RNA-seq was performed.Analysis of the sequencing results showed that 15 signaling pathways were involved in the regulation.In order to verify whether the relevant signal pathways are involved in regulation,the signal pathways with more enriched genes involved in the lithium salt treatment and the lithium salt and CHX co-treatment were classified into nine signal pathways after the commonality classification,and the specific signal pathway inhibitors were used for experimental verification.Experimental verification can provide some theoretical basis for the study of the molecular mechanism of lithium to up-regulate the biological clock gene per2,and also provide some new theoretical basis for the treatment of bipolar disorder.