Siwen Gui1, Yiyun Liu2, Juncai Pu2, Xuemian Song1, Xiaopeng Chen3, Weiyi Chen3, Xiaogang Zhong4, Haiyang Wang4, Lanxiang Liu5, Peng Xie6. 1. College of Biomedical Engineering, Chongqing Medical University, Chongqing 40016, China; State Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing 40016, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. 2. NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. 3. NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. 4. College of Stomatology and Affiliated Stomatological Hospital of Chongqing Medical University, Chongqing 401147, China. 5. Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China. 6. NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: xiepeng@cqmu.edu.cn.
Abstract
BACKGROUND: Major depressive disorder (MDD) is a psychiatric disorder caused by various etiologies. Chronic stress models are used to simulate the heterogeneous pathogenic processes of depression. However, few studies have compared transcriptional features between stress models and MDD patients. METHODS: We generated hippocampal transcriptional profiles of the chronic social defeat model by RNA sequencing and downloaded raw data of the same brain region from public databases of the chronic unpredictable mild stress model, the learned helplessness model, and MDD patients. Differential expression and gene co-expression analyses were integrated to compare transcriptional features between stress models and MDD patients. RESULTS: Each stress model shared 11.4% to 16.3% of differentially expressed genes with MDD patients. Functional analysis at the gene expression level identified altered ensheathment of neurons in both stress models and MDD patients. At the gene network level, each stress model shared 20.9% to 41.6% of co-expressed genes with MDD patients. Functional analysis based on these genes found that axon guidance signaling is the most significantly enriched pathway that was shared by all stress models and MDD patients. LIMITATIONS: This study was limited by considering only a single brain region and a single sex of stress model animals. CONCLUSIONS: Our results show that hippocampal transcriptional features of stress models partially overlap with those of MDD patients. The canonical pathways of MDD patients, including ensheathment of neurons, PTEN signaling, and axonal guidance signaling, were shared with all stress models. Our findings provide further clues to understand the molecular mechanisms of depression.
BACKGROUND: Major depressive disorder (MDD) is a psychiatric disorder caused by various etiologies. Chronic stress models are used to simulate the heterogeneous pathogenic processes of depression. However, few studies have compared transcriptional features between stress models and MDDpatients. METHODS: We generated hippocampal transcriptional profiles of the chronic social defeat model by RNA sequencing and downloaded raw data of the same brain region from public databases of the chronic unpredictable mild stress model, the learned helplessness model, and MDDpatients. Differential expression and gene co-expression analyses were integrated to compare transcriptional features between stress models and MDDpatients. RESULTS: Each stress model shared 11.4% to 16.3% of differentially expressed genes with MDDpatients. Functional analysis at the gene expression level identified altered ensheathment of neurons in both stress models and MDDpatients. At the gene network level, each stress model shared 20.9% to 41.6% of co-expressed genes with MDDpatients. Functional analysis based on these genes found that axon guidance signaling is the most significantly enriched pathway that was shared by all stress models and MDDpatients. LIMITATIONS: This study was limited by considering only a single brain region and a single sex of stress model animals. CONCLUSIONS: Our results show that hippocampal transcriptional features of stress models partially overlap with those of MDDpatients. The canonical pathways of MDDpatients, including ensheathment of neurons, PTEN signaling, and axonal guidance signaling, were shared with all stress models. Our findings provide further clues to understand the molecular mechanisms of depression.