title: Paeoniflorin ameliorates interferon-alpha-induced neuroinflammation and depressive-like behaviors in mice.
abstract: Long-term treatment with high-dose Interferon-alpha (IFN-α) has resulted in depression in 30-50% of the patients. Paeoniflorin may ameliorate the IFN-α-induced depression; however, the underlying mechanism is less studied. Here, we investigated the prophylactic antidepressant and anti-neuroinflammatory effects of paeoniflorin on the behaviors and specific emotion-related regions of the brain in mice with IFN-α-induced depression. A series of behavior assessments were conducted to identify the depressive state after subcutaneously IFN-α injections and with or without intragastrically paeoniflorin administration in C57BL/6J mice. Levels of many inflammatory-related cytokines in serum, mPFC, vHi and amygdala were determined by cytokine array analysis. Furthermore, microglia and astrocyte activation in these three regions were evaluated by immunohistochemistry. We found that the mice which were subcutaneously injected IFN-α 15×106 IU/kg for 4 successive weeks to mimic an IFN-α-induced depression model had distinct inflammatory changes in the amygdala. Interestingly, 4-week 20 mg/kg or 40 mg/kg paeoniflorin pretreatments reversed the depressive-like behaviors and the abnormal inflammatory cytokine levels in the serum, mPFC, vHi and amygdala. These cytokines were not limited to the commonly reported IL-6, IL-1β and TNF-α, but also IL-9, IL-10, IL-12, and MCP-1. Besides, the increased density of microglia in IFN-α-treated mice was reversed by paeoniflorin in these three brain areas. Taken together, our data suggest that paeoniflorin can reverse the long-term, high-dose IFN-α-induced depressive-like behaviors that were associated with local distinct neuroinflammation in the mPFC, vHi and particularly the amygdala. Paeoniflorin might have a preventive therapeutic potential in IFN-α-induced depression.
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Shaohui
authors.initials: S
authors.lastname: Huang
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Huang
authors.affiliation: Experimental Animal Center, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Wanshan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Medical Imaging Department, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Wen
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, 999077, China.
authors.forename: Xiuqiong
authors.initials: X
authors.lastname: Fu
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Wang
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Weihai
authors.initials: W
authors.lastname: Liang
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, 999077, China.
authors.forename: Hiu Yee
authors.initials: HY
authors.lastname: Kwan
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Lv
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D003863:Depression / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control* / Q000523:psychology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D005518:Food Preferences / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008297:Male; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D039821:Monoterpenes / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D011994:Recombinant Proteins; D013550:Swimming; D013997:Time Factors; D006027:Glycosides
chemical_list: D000893:Anti-Inflammatory Agents; D000928:Antidepressive Agents; D016207:Cytokines; D005960:Glucosides; D018836:Inflammation Mediators; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D039821:Monoterpenes; D011994:Recombinant Proteins; C015423:peoniflorin; D006027:Glycosides
keywords: amygdala; depression; interferon; neuroinflammation; paeoniflorin