Gene Expression Profiling of the Habenula in Rats Exposed to Chronic Restraint Stress

Abstract

Chronic stress contributes to the risk of developing depression; the habenula, a nucleus in epithalamus, is associated with many neuropsychiatric disorders. Using genome-wide gene expression analysis, we analyzed the transcriptome of the habenula in rats exposed to chronic restraint stress for 14 days. We identified 379 differentially expressed genes (DEGs) that were affected by chronic stress. These genes were enriched in neuroactive ligand-receptor interaction, the cAMP (cyclic adenosine monophosphate) signaling pathway, circadian entrainment, and synaptic signaling from the Kyoto Encyclopedia of Genes and Genomes pathway analysis and responded to corticosteroids, positive regulation of lipid transport, anterograde trans-synaptic signaling, and chemical synapse transmission from the Gene Ontology analysis. Based on protein–protein interaction network analysis of the DEGs, we identified neuroactive ligand-receptor interactions, circadian entrainment, and cholinergic synapse-related subclusters. Additionally, cell type and habenular regional expression of DEGs, evaluated using a recently published single-cell RNA sequencing study (GSE137478), strongly suggest that DEGs related to neuroactive ligand-receptor interaction and trans-synaptic signaling are highly enriched in medial habenular neurons. Taken together, our findings provide a valuable set of molecular targets that may play important roles in mediating the habenular response to stress and the onset of chronic stress-induced depressive behaviors.

Encore: Behavioural animal models of stress, depression and mood disorders

“…Such findings are contrary to the observations in human patients and mice that undergo other stress paradigms ( Stetler and Miller, 2011 ). Recent findings have identified the effects that CRS shares with other paradigms and that mirror those observed in humans ( Yuen et al, 2012 ; Seewoo et al, 2020 ; Yoo et al, 2022 ). For example both CRS and CSDS induce elevated firing in the projection from the lateral hypothalamus to the LHb which causes the onset of depressive-like symptoms ( Zheng et al, 2022 ).…”

Bacillus coagulans and Clostridium butyricum synergistically alleviate depression in a chronic unpredictable mild stress mouse model through altering gut microbiota and prefrontal cortex gene expression

“…Gok Oguz et al analyzed the apelin level in peritoneal dialysis (PD) patients with depression and anxiety and found that it was significantly greater than that in PD patients without depression and anxiety (Gok Oguz et al, 2016). A previous study also revealed DEGs related to neuroactive ligand-receptor interactions in a chronic restraint stress (CRS) rat model (Yoo et al, 2022). The calcium signaling pathway was also enriched in CUMS models and depression patients (Kao et al, 2012;Chen et al, 2023).…”

Potential role of LPAR5 gene in prognosis and immunity of thyroid papillary carcinoma and pan-cancer

“…Stress has negative effects on both the neuroendocrine system and the sympathetic nervous system (SNS) of the body, which is manifested by continuous activation of the hypothalamic–pituitary–adrenal (HPA) axis and SNS, thus increasing catecholamine secretion, promoting tumor cell proliferation and metastasis, and enhancing angiogenesis 29 , 32 , 33 . Neuroactive ligand-receptor interactions are thought to be a key factor involved in emotion-related disorders 34 – 36 , and stress runs through these disorders. Wen et al found that oxidative stress is involved in the pathogenesis process of PTC 37 .…”