Transcriptome comparative analysis of amygdala-hippocampus in depression: A rat model induced by chronic unpredictable mild stress (CUMS)

Background: Depression is a common and complex mental disease, and its pathogenesis involves several brain regions. Abnormalities in the amygdala-hippocampal neural circuits have been shown to be involved in depression. However, the underlying molecular mechanisms remain unclear.Methods: A rat model was used to determine the transcriptome changes in the amygdala-hippocampal neural network under chronic unpredictable mild stress (CUMS). Depression-related modules in this neural network were identified using weighted gene co-expression network analysis (WGCNA). Difference and enrichment an-alyses were used to determine differential gene expression in the two brain regions.Results: The modules in the amygdala and hippocampus associated with depression-like behavior contained 363 and 225 genes, respectively. Forty-two differentially expressed genes were identified in the amygdala candidate module and 37 in the hippocampus. Enrichment analysis showed that candidate genes in the amygdala were associated with neuronal myelination and candidate genes in the hippocampus were associated with synaptic transmission. Finally, based on module hub gene statistics, differential gene expression, and protein-protein interaction networks, 11 central genes were found in the amygdala candidate module, and one central gene was found in the hippocampal module. Limitations: Our study was based on a rat CUMS model. Further evidence is needed to prove that our results are applicable to patients with depression.Conclusion: This study identified critical modules and central genes involved in the amygdala-hippocampal cir-cuit in the context of depression, and may provide further understanding of the pathogenesis of depression and help identify potential targets for antidepressant therapy.