Genetic deletion of GluN3A affects depression-like behaviors and mRNA transcriptome in medial prefrontal cortex and hippocampus in mice

Autor: ZHANG Mengmeng, LIU Wenqin, CHEN Jing, KONG Xiangru
Jazyk: čínština
Rok vydání: 2023
Předmět:
Zdroj: 陆军军医大学学报, Vol 45, Iss 15, Pp 1641-1650 (2023)
Druh dokumentu: article
ISSN: 2097-0927
DOI: 10.16016/j.2097-0927.202302053
Popis: Objective To explore the potential molecular mechanism of GluN3A gene deletion involved in depression-like behaviors. Methods Fourteen male adult GluN3A knockout (KO) mice and 15 male wild type (WT) mice were recruited in this study. Sucrose preference test (SPT) and forced swim test (FST) were conducted to measure depression-like behaviors. Then tissue samples of medial prefrontal cortex (mPFC) and hippocampus (HP) were collected from 5 mice in each group for mRNA transcriptome sequencing. Differentially expressed genes (DEGs) were screened using DESeq2 software, and some DEGs were selected and validated by qPCR. Gene Ontology (GO) enrichment analysis was performed using clusterProfiler software. Protein interaction network analysis was performed using string online database together with Cytoscape software. Results GluN3A KO mice exhibited decreased sucrose preference (P < 0.05) and sucrose consumption (P < 0.05) in FST and prolonged immobile time (P < 0.01) in FST. There were 740 and 666 DEGs found in the mPFC and the hippocampus of GluN3A KO mice, respectively. GO analysis showed that down-regulated DEGs in the mPFC were enriched in angiogenesis and neural precursor cell proliferation, while down-regulated DEGs in the hippocampus were mainly enriched in synapse assembly, axon development, dendrite development, axon guidance and synaptic membrane. And up-regulated DEGs in both mPFC and hippocampus were mainly associated with cytosolic ribosome and ribosomal subunit. Protein interaction network analysis revealed that most of the core genes in the mPFC and hippocampus were ribosomal protein genes. Conclusion GluN3A deletion may be involved in the occurrence of depression-like behaviors by regulating angiogenesis, neural precursor cell proliferation, synapse formation and protein synthesis.
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