The Effects And Mechanism Of Dusp27 On Emotional And Cognitive Function In Mice

Pseudo Dual specificity phosphatase 27(Dusp27)gene is located on mouse chromosome 1,which is mainly highly expressed in skeletal muscle and myocardium.Its encoding protein is one of the only the pseudophosphatases in the DUSP family.The catalytic cysteine at position 120 in the amino acid sequence of Dusp27 is replaced by glycine,which loses the dual catalytic activity of dephosphorylation of threonine / serine and tyrosine residues of the substrate protein molecule.However,DUSP27 can still interfere with the downstream substrates by binding to the substrates phosphorylation site or other molecular pathways,and to regulate multiple signaling pathways.Recent studies have also found that Dusp27 is also expressed in the prefrontal cortex,hippocampus,cerebellum and other central nervous system tissues,suggesting that the gene may be involved in the functional regulation of the nervous system.In the previous work of this study,it was found that Dusp27 knockout mice showed homozygous(Dusp27-/-)lethality.Based on this,wild-type(WT)and heterozygous(Dusp27+/-)mice were used as research objects in this paper.Behavioral techniques such as open field experiments and new object recognition experiments were used to observe whether Dusp27 was involved in the regulation of emotional and cognitive levels in mice.At the same time,fluorescence in situ hybridization and fluorescence quantitative PCR were used to further detect the expression level of Dusp27 in the prefrontal cortex and hippocampus of mice.Then,high-throughput sequencing and bioinformatics analysis were used to compare and explore the enrichment of differentially expressed genes in the prefrontal cortex and hippocampus of WT mice and Dusp27+/-mice,and analyze the related signal transduction pathways.The aim for this study is to explore the possible molecular mechanism of Dusp27 affecting the emotional and cognitive changes in mice.The results are as follows:1)The results of behavioral experiments showed that compared with WT mice,Dusp27+/-mice significantly reduced the number of grid crossings in the central area of the open field,significantly prolonged the rest time,and significantly shortened the horizontal movement distance,suggesting that the change of Dusp27 expression level will affect the emotional and emotional expression of mice,weaken their willingness to act,increase negative emotions,and show a tendency of depression;on the other hand,compared with WT mice,the residence time of Dusp27+/-mice in the central area of the open field was also significantly shortened,the number of uprights was significantly reduced,and the cognitive index was significantly reduced,suggesting that altered cognitive abilities in Dusp27+/-mice,manifested as reduced spontaneous behavior and reduced willingness to explore unknown environments.2)The results of fluorescence in situ hybridization showed that Dusp27 was expressed in the prefrontal cortex and hippocampus of both types of mice,and the expression level in Dusp27+/-mice was significantly lower than that in WT mice;the results of fluorescence quantitative PCR further confirmed the above experimental results.Combined with the results of behavioral experiments in this experiment,it is suggested that the decrease of Dusp27 expression level in the prefrontal cortex and hippocampus will affect the emotional and emotional expression of Dusp27+/-mice,resulting in an increase in negative emotions and a decrease in spontaneous behavior and cognitive level.3)Bioinformatics analysis for mRNA sequencing results showed in the prefrontal cortex and hippocampus,compared with WT mice,Dusp27+/-mice enriched multiple differentially expressed genes such as ADORA2 A,FGF3,TACR1,HSPA1 A,XBP1,HSPA5,etc.In the prefrontal cortex,the differentially expressed genes are mainly enriched in calcium signaling,c AMP signaling and cancer signaling pathways;in the hippocampus,the differentially expressed genes mainly enriched in PI3K-Akt signaling and lipid and atherosclerosis signaling pathways.Conclusion: This study revealed that Dusp27+/-mice exhibit changes in mood and cognitive function in comparison to WT mice.These alterations are assoicated with the decreased expression of the Dusp27 gene in the prefrontal cortex and hippocampus.The possible mechanism is that reduced expression of Dusp27,resulting in downstream genes differentially expressed,most of the genes are up-regulated and a few of genes are down-regulated.These differential expressed genes are enriched in multiple key signaling pathways,which are potential mechanism underlying Dusp27 in the prefrontal cortex and hippocampus regulation of mice emotional and cognitive activities.