Jingjie Zhao1, Xuesong Gao2, Anna Wang2, Yongzhi Wang3, Yi Du4, Li Li2, Mingzhen Li5, Chong Li6, Xiaoying Jin7, Mei Zhao8. 1. CAS, Key Lab of Mental Health, Institute of Psychology, Beijing 100101, China; Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China. 2. Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China. 3. Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China. Electronic address: wangyongzhi_1978@sina.com. 4. Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China. Electronic address: dodo_8110@aliyun.com. 5. CAS, Key Lab of Mental Health, Institute of Psychology, Beijing 100101, China. 6. CAS, Key Lab of Mental Health, Institute of Psychology, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 101408, China. Electronic address: 793539816@qq.com. 7. CAS, Key Lab of Mental Health, Institute of Psychology, Beijing 100101, China. Electronic address: kingyy0128@live.com. 8. CAS, Key Lab of Mental Health, Institute of Psychology, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 101408, China. Electronic address: zhaomei@psych.ac.cn.
Abstract
BACKGROUND: Recent studies have indicated that inflammatory pathways and hypothalamic-pituitary-adrenal (HPA) axis function may be responsible for the interaction between pain and depression. METHODS: Animals were examined for depressive and painful behavior following exposure to chronic unpredictable mild stress (CUMS) and chronic corticosterone (CORT) treatment. Subsequently, serum cytokines, adrenocorticotropic hormone (ACTH) and CORT were measured by enzyme-linked immunosorbent assay (ELISA). mRNA expression of cytokines in the brain were measured by quantitative PCR (qPCR). RESULTS: The present study found that both CUMS and chronic CORT treatment induced behavioral changes of depression comorbid hyperalgesia. Moreover, both the treatments increased levels of serum ACTH, CORT, and cytokines including tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL1ß), interleukin 6 (IL6), and Caspase 1 (CASP1). Following CUMS, Il1ß levels were found to be elevated in all examined regions, including the raphe nuclei, thalamus, hippocampus, prefrontal cortex, and pituitary. In the raphe nuclei particularly, CUMS elevated all examined cytokine levels. Chronic CORT treatment, however, produced Il1ß elevation in the hippocampus and the pituitary, with showing elevated levels in all examined cytokines. LIMITATION: To clarify the causal relationship between behavioral changes and altered cytokine levels via either antidepressant treatment or blockage of pre-inflammatory cytokine production, further studies should be conducted. CONCLUSIONS: Despite similar behavioral consequences, hypercortisolism and peripheral inflammation, CUMS and chronic CORT treatment seem to produce differing inflammatory brain responses.
BACKGROUND: Recent studies have indicated that inflammatory pathways and hypothalamic-pituitary-adrenal (HPA) axis function may be responsible for the interaction between pain and depression. METHODS: Animals were examined for depressive and painful behavior following exposure to chronic unpredictable mild stress (CUMS) and chronic corticosterone (CORT) treatment. Subsequently, serum cytokines, adrenocorticotropic hormone (ACTH) and CORT were measured by enzyme-linked immunosorbent assay (ELISA). mRNA expression of cytokines in the brain were measured by quantitative PCR (qPCR). RESULTS: The present study found that both CUMS and chronic CORT treatment induced behavioral changes of depression comorbid hyperalgesia. Moreover, both the treatments increased levels of serum ACTH, CORT, and cytokines including tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL1ß), interleukin 6 (IL6), and Caspase 1 (CASP1). Following CUMS, Il1ß levels were found to be elevated in all examined regions, including the raphe nuclei, thalamus, hippocampus, prefrontal cortex, and pituitary. In the raphe nuclei particularly, CUMS elevated all examined cytokine levels. Chronic CORT treatment, however, produced Il1ß elevation in the hippocampus and the pituitary, with showing elevated levels in all examined cytokines. LIMITATION: To clarify the causal relationship between behavioral changes and altered cytokine levels via either antidepressant treatment or blockage of pre-inflammatory cytokine production, further studies should be conducted. CONCLUSIONS: Despite similar behavioral consequences, hypercortisolism and peripheral inflammation, CUMS and chronic CORT treatment seem to produce differing inflammatory brain responses.
Authors: Yu Zheng; Ming Gao; Guangdong Hou; Niuniu Hou; Xiao Feng; Tommaso B Jannini; Di Wei; Wanxiang Zheng; Lei Zhang; Xinlong Dun; Geng Zhang; Fuli Wang; Ping Meng; Emmanuele A Jannini; Jianlin Yuan Journal: Front Public Health Date: 2022-06-17