Study Of Expression,activity And Function Of SRC3 In Mouse Forebrain

Steroid receptor coactivators（SRC）are an important class of transcriptional regulators.SRC1,SRC2,and SRC3 of the SRC family have a high degree of homology.They mainly include nuclear receptor binding domain and transcription factor binding domain,which can bind with steroid receptors and other nuclear receptors and regulate gene transcription.And only SRC3 has acetyltransferase activity.SRC3 is mainly expressed in the hippocampus,cortex and olfactory bulb,and can regulate the pain perception ability and motor coordination ability of mice,as well as the anxiety response of female mice.In the past,there have been many studies on the expression and function of SRC in the brain,but there are few studies on SRC3.Although we have known that SRC are mainly expressed in the hippocampus,cortex,and hypothalamus,the expression of the subcellular distribution in neurons has not been studied in detail,nor has it been studied to regulate functions other than anxiety,motor coordination,and pain perception.In order to clarify these issues,we first analyzed the single-cell RNA sequencing results of human cerebral cortex and mouse forebrain through the database,and described the expression of SRC in the cells of various regions.Then by subcellular component separation and Western blotting we detected that SRC1 and SRC2 are only distributed in the nucleus of neurons,while SRC3 is mainly distributed in the cytoplasm and synapse.And then we used the database to analyze that SRC3expression increased with the development of mice and it is mainly expressed in the forebrain.We also used the database to analyze the distribution of SRC3 in different cells of the hippocampus,and concluded that SRC3 is abundantly express in CA3 and CA1.By constructing an ELISA kit,we found that neural activity cLTP can promote the acetyltransferase activity of SRC3.Finally,we used Src3^+/-mice to conduct a series of learning and memory behavioral tests,and through T maze and Y maze,it is found that the working memory of Src3^+/-mice is not significantly different from that of WT mice,but the social hierarchy is significantly reduced,indicating that SRC3participates in the social hierarchy formation of mice,which laid a foundation for further research on the mechanism of SRC3 participating in the social hierarchy of mice.In summary,we found that in the SRC family,SRC3 mainly exists in the cytoplasm and synapse of neurons,and the activity of SRC3 acetyltransferase is regulated by neural activity.Finally,SRC3 participates in the formation of social hierarchy of mice.These provide some guidance for the future study of SRC’s role in synaptic plasticity,learning and memory,and related mental diseases.