Tianlan Lan1, Mengge Bai2, Xiangyu Chen3, Yue Wang4, Yan Li3, Yu Tian3, Yong He3, Zhonghao Wu1, Heming Yu3, Zhi Chen3, Chong Chen5, Yaping Yu5, Ke Cheng6, Peng Xie7. 1. NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing Medical University, Chongqing 400016, China; College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China. 2. NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing Medical University, Chongqing 400016, China; Key Laboratory of Laboratory Medical Diagnostics designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China. 3. Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing Medical University, Chongqing 400016, China. 4. NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience, Basic Medical College, Chongqing Medical University, Chongqing 400016, China. 5. NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing Medical University, Chongqing 400016, China. 6. Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience, Basic Medical College, Chongqing Medical University, Chongqing 400016, China. Electronic address: jackchengke@163.com. 7. Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing Medical University, Chongqing 400016, China. Electronic address: xiepeng@cqmu.edu.cn.
Abstract
AIMS: Major depressive disorder, as a destructive mental health disorder, is a major contributor to disability and death. Numerous studies have illustrated that activation of inflammation and fluctuating immune reactions play a crucial role in the physiopathology of depression. The effectiveness of antidepressants is affected by the intensity of the inflammatory response. Thus, we aim to reveal the correlation of inflammatory factors and depression. MAIN METHODS: Isobaric tags for relative and absolute quantitation (iTRAQ™)-based proteomics was applied to verify the quantitation of target proteins in the PFC of chronic social defeat stress (CSDS) model mice. Ingenuity pathway analysis (IPA) was performed to explore related pathways, and the involvement of molecules was validated by western blotting and real time-quantitative polymerase chain reaction (RT-qPCR). KEY FINDINGS: According to the IPA results, CSDS-susceptible mice and CSDS-resilient mice both exhibited alterations of the inflammasome pathway in the PFC. Compared with control mice, susceptible mice subjected to CSDS showed an increased ATP-activated purinergic receptor P2X7 (also known as P2RX7) protein level. Nevertheless, the expression levels of cysteinyl aspartate-specific protease 1 (Caspase 1) and apoptosis-associated speck-like protein containing a CARD (ASC) were reduced in CSDS mice, and downregulation of interleukin-1β (IL-1β) was found in susceptible mice. Moreover, no significant difference was found in nuclear factor-κB levels among the three groups. SIGNIFICANCE: CSDS administration leads to dysfunctions of key molecules in the inflammasome pathway, promoting depressive-like behaviors in mice.
AIMS: Major depressive disorder, as a destructive mental health disorder, is a major contributor to disability and death. Numerous studies have illustrated that activation of inflammation and fluctuating immune reactions play a crucial role in the physiopathology of depression. The effectiveness of antidepressants is affected by the intensity of the inflammatory response. Thus, we aim to reveal the correlation of inflammatory factors and depression. MAIN METHODS: Isobaric tags for relative and absolute quantitation (iTRAQ™)-based proteomics was applied to verify the quantitation of target proteins in the PFC of chronic social defeat stress (CSDS) model mice. Ingenuity pathway analysis (IPA) was performed to explore related pathways, and the involvement of molecules was validated by western blotting and real time-quantitative polymerase chain reaction (RT-qPCR). KEY FINDINGS: According to the IPA results, CSDS-susceptible mice and CSDS-resilient mice both exhibited alterations of the inflammasome pathway in the PFC. Compared with control mice, susceptible mice subjected to CSDS showed an increased ATP-activated purinergic receptor P2X7 (also known as P2RX7) protein level. Nevertheless, the expression levels of cysteinyl aspartate-specific protease 1 (Caspase 1) and apoptosis-associated speck-like protein containing a CARD (ASC) were reduced in CSDS mice, and downregulation of interleukin-1β (IL-1β) was found in susceptible mice. Moreover, no significant difference was found in nuclear factor-κB levels among the three groups. SIGNIFICANCE: CSDS administration leads to dysfunctions of key molecules in the inflammasome pathway, promoting depressive-like behaviors in mice.
Authors: Malena Dos Santos Guilherme; Francesco Valeri; Jennifer Winter; Marianne B Müller; Andreas Schwiertz; Kristina Endres Journal: Microorganisms Date: 2022-05-24