Objective:To identify core genes with co-expression trends in the suprachiasmatic nucleus (SCN) and lateral habenula (LHb) through miRNA sequencing, and to explore the molecular mechanisms underlying the onset and progress of sleep disturbances in depression.Methods:A rat model of depression with sleep disturbances was established. Behavioral assessments were conducted using the pentobarbital-induced sleep test, sucrose water consumption test, and open field test. Differentially expressed genes (DEGs) in the SCN and LHb of model rats were analyzed using biological replicates with the limma package and DESeq2 software. Gene ontology (GO), KEGG, Reactome pathway-gene set enrichment analysis (GSEA) were performed on the DEGs.Co-expression networks and protein-protein interaction (PPI) networks were constructed using R and Cytoscape software for further screening of genes with potential regulatory roles.Results:After modeling, the sleep latency in the model group ((679.88±350.05) s) was longer than that in the normal group ((316.25±87.35) s) ( t=-2.851, P=0.022), while the sleep duration in the model group ((33.13±8.41) min) was shorter than that in the normal group ((69.72±25.11) min) ( t=3.907, P=0.004). Additionally, the model group exhibited lower sucrose water consumption, horizontal movement counts, and vertical movement counts compared to the normal group (all P<0.05). Differential expression gene analysis showed, in the SCN, 379 genes were upregulated and 132 genes were downregulated, with the top five most significantly differentially expressed genes being Sec61g, Cox6b1, Ephx2, Thrsp, and Pak2. In the LHb, 1 657 genes were upregulated and 1 737 were downregulated, with the top five most significantly differentially expressed genes being Mrpl32, Mrpl20, Mrpl27, Celsr2, and Uba52. Biological pathways enriched in the SCN were mainly associated with the positive regulation of responses to external and biological stimuli. In contrast, pathways enriched in the LHb were related to neurotransmitter level regulation, developmental growth, neurotransmitter transport, and processes such as learning and memory. Co-expression network analysis identified 864 interactions involving 100 nodes in the SCN and 524 interactions involving 99 nodes in the LHb. Conclusion:The biological functions and signaling pathways of the suprachiasmatic nucleus and lateral habenula are different in the occurrence and development of depression with sleep disturbance, and the significantly differentially expressed genes may play an important role.

Objective:To identify core genes with co-expression trends in the suprachiasmatic nucleus (SCN) and lateral habenula (LHb) through miRNA sequencing, and to explore the molecular mechanisms underlying the onset and progress of sleep disturbances in depression.Methods:A rat model of depression with sleep disturbances was established. Behavioral assessments were conducted using the pentobarbital-induced sleep test, sucrose water consumption test, and open field test. Differentially expressed genes (DEGs) in the SCN and LHb of model rats were analyzed using biological replicates with the limma package and DESeq2 software. Gene ontology (GO), KEGG, Reactome pathway-gene set enrichment analysis (GSEA) were performed on the DEGs.Co-expression networks and protein-protein interaction (PPI) networks were constructed using R and Cytoscape software for further screening of genes with potential regulatory roles.Results:After modeling, the sleep latency in the model group ((679.88±350.05) s) was longer than that in the normal group ((316.25±87.35) s) ( t=-2.851, P=0.022), while the sleep duration in the model group ((33.13±8.41) min) was shorter than that in the normal group ((69.72±25.11) min) ( t=3.907, P=0.004). Additionally, the model group exhibited lower sucrose water consumption, horizontal movement counts, and vertical movement counts compared to the normal group (all P<0.05). Differential expression gene analysis showed, in the SCN, 379 genes were upregulated and 132 genes were downregulated, with the top five most significantly differentially expressed genes being Sec61g, Cox6b1, Ephx2, Thrsp, and Pak2. In the LHb, 1 657 genes were upregulated and 1 737 were downregulated, with the top five most significantly differentially expressed genes being Mrpl32, Mrpl20, Mrpl27, Celsr2, and Uba52. Biological pathways enriched in the SCN were mainly associated with the positive regulation of responses to external and biological stimuli. In contrast, pathways enriched in the LHb were related to neurotransmitter level regulation, developmental growth, neurotransmitter transport, and processes such as learning and memory. Co-expression network analysis identified 864 interactions involving 100 nodes in the SCN and 524 interactions involving 99 nodes in the LHb. Conclusion:The biological functions and signaling pathways of the suprachiasmatic nucleus and lateral habenula are different in the occurrence and development of depression with sleep disturbance, and the significantly differentially expressed genes may play an important role.