Interferon-α exacerbates neuropsychiatric phenotypes in lupus-prone mice

被引:16
|
作者
Zeng, Jing [1 ]
Meng, Xinyu [1 ]
Zhou, Ping [1 ]
Yin, Zhihua [2 ]
Xie, Qinglian [3 ]
Zou, Hong [3 ]
Shen, Nan [1 ,2 ,3 ,4 ,5 ,6 ]
Ye, Zhizhong [2 ]
Tang, Yuanjia [1 ,2 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Inst Rheumatol, 145 Shan Dong Rd C, Shanghai, Peoples R China
[2] Shenzhen Futian Hosp Rheumat Dis, 22 Nong Lin Rd, Shenzhen, Peoples R China
[3] Univ Chinese Acad Sci, CAS, SIBS, 320 Yueyang Rd, Shanghai, Peoples R China
[4] Renji Hosp, Shanghai Canc Inst, State Key Lab Oncogenes & Related Genes, 2200 Lane 25 Xietu Rd, Shanghai, Peoples R China
[5] Shanghai Jiao Tong Univ, Sch Med, Collaborat Innovat Ctr Translat Med, 197 Rui Jin Er Rd, Shanghai, Peoples R China
[6] Cincinnati Childrens Hosp Med Ctr, CAGE, 3333 Burnet Ave, Cincinnati, OH 45229 USA
基金
中国国家自然科学基金;
关键词
Lupus; Autoimmunity; Cytokines; Neuropsychiatric SLE (NP-SLE); IFN-ALPHA; ERYTHEMATOSUS; MODEL; GENE; ANXIETY; MANIFESTATIONS; BEHAVIOR; DISEASE; MEMORY; TASK;
D O I
10.1186/s13075-019-1985-9
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Neuropsychiatric systemic lupus erythaematosus (NP-SLE) is one of the major manifestations of lupus. However, the mechanisms involved in NP-SLE are still largely unknown. The abnormal activation of the type I IFN signalling pathway is involved in SLE pathogenesis and is linked to NP-SLE, but the effect of IFN-alpha on NP-SLE encephalopathy has not been systematically studied. Methods An intravenous injection of Adv-IFN-alpha (10 mice, 10 x 10(9) vp) was administered to the IFN-alpha-treated group, and Adv-ctrl (10 mice, 10 x 10(9) vp) (ViGene Biosciences, China) was administered to the control group. Gene expression was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies in the serum, and urinary protein levels were measured with a BCA Protein Assay kit. Haematoxylin-eosin (H&E) and periodic acid-Schiff (PAS)-light green staining were used for kidney histology. The elevated plus-maze test, novelty-suppressed feeding assay, open-field test, tail suspension test, social dominance tube test, three-chamber social interaction test, step-down passive avoidance test and novelty Y-maze task were used to assess behaviour. Results In this study, we performed a series of behavioural tests to assess the neuropsychiatric phenotypes of IFN-alpha-treated NZB/NZW F1 mice and found that these mice developed a series of mental disorders such as anxiety-like phenotypes, depression-like phenotypes, deficits in sociability and cognitive impairments, which mimic the neuropsychiatric manifestations of NP-SLE, with a consistent onset and progression. Conclusions Our research verified that IFN-alpha plays a critical role in NP-SLE and provides a comprehensive NP-SLE mouse model for dissecting the mechanisms of NP-SLE and developing novel therapies for intervention.
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页数:11
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