The role of vitamin D: a promising pathway to combat neuropsychiatric lupus disorders.

IF 3.4 3区 医学 Q3 IMMUNOLOGY
Thaís Evelyn Karnopp, Gustavo Flores Chapacais, Maria Luísa Gasparini, Natália Garcia Dos Santos, Vinicius da Silva Freitas, Marina Piccoli, Andressa Leite Di Domenico, Lucas Denardi Doria, Nikolas Mateus Pereira de Souza, Alexandre Rieger, Eduarda Correa Freitas, Fernanda Visioli, Odirlei André Monticielo
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Abstract

To evaluate neuropsychiatric manifestations in the pristane-induced lupus (PIL) model, as well as to evaluate immunoregulatory effects of vitamin D (vit-D) in the brain of mice with PIL. Eighty female BALB/c mice were divided into six groups with 90 (3 months) and 180 (6 months) days of experimentation: CO3, CO6 (controls), PIL3, PIL6 (pristane-induced lupus), VD3 and VD6 (PIL supplemented with 1,25-dihydroxyvitamin D). Forced-swim, elevated plus maze and Barnes maze were the behavioral tests performed. Expression of pVDR was assessed by immunofluorescence. Brain IgM and IgG deposits were evaluated by double staining fluorescence. Serum IL-6 and IFN-α1 were quantified by ELISA. AUC-ROC curve was also performed for immunoglobulins. PIL and VD showed depressive-like behavior in the forced-swim test and anxious-like behavior in the elevated plus maze test. PIL also presented cognitive and memory impairment in the Barnes maze test. Additionally, PIL and VD presented higher levels of serum IFN-α1, but not IL-6. Mice supplemented with vit-D had reduced IgM and IgG deposits and increased pVDR expression in the brain after 180 days. The AUC-ROC curve demonstrated high sensitivity and specificity for IgM and IgG in the brain. We observed neuropsychiatric manifestations in this model of systemic lupus erythematosus (SLE), strongly corroborating to PIL model being suitable as a neuropsychiatric lupus (NPSLE) model. Vit-D was able to reduce immunoglobulin deposits in the brain and influenced the levels of serum IL-6 in the animals assessed. Also, it improved memory, but it had no effect on depressive and anxious-like behavior.

维生素 D 的作用:防治神经精神狼疮疾病的有效途径。
评估普里斯坦诱导狼疮(PIL)模型的神经精神表现,并评估维生素 D(vit-D)对 PIL 小鼠大脑的免疫调节作用。80 只雌性 BALB/c 小鼠被分为 6 组,实验天数分别为 90 天(3 个月)和 180 天(6 个月):CO3、CO6(对照组)、PIL3、PIL6(普里斯坦诱导的狼疮)、VD3 和 VD6(补充 1,25-二羟维生素 D 的 PIL)。进行的行为测试包括强迫游泳、高架迷宫和巴恩斯迷宫。免疫荧光评估了 pVDR 的表达。脑IgM和IgG沉积物通过双重荧光染色进行评估。血清IL-6和IFN-α1通过ELISA进行定量。还对免疫球蛋白进行了AUC-ROC曲线分析。PIL和VD在强迫游泳测试中表现出抑郁样行为,在高架加迷宫测试中表现出焦虑样行为。PIL 还在巴恩斯迷宫测试中表现出认知和记忆障碍。此外,PIL 和 VD 的血清 IFN-α1 水平较高,但 IL-6 水平不高。180 天后,补充维生素 D 的小鼠脑内 IgM 和 IgG 沉积减少,pVDR 表达增加。AUC-ROC曲线显示了大脑中IgM和IgG的高灵敏度和特异性。我们在该系统性红斑狼疮(SLE)模型中观察到了神经精神表现,这有力地证明了 PIL 模型适合作为神经精神狼疮(NPSLE)模型。Vit-D 能够减少大脑中的免疫球蛋白沉积,并影响被评估动物的血清 IL-6 水平。此外,它还能改善记忆力,但对抑郁和焦虑行为没有影响。
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来源期刊
CiteScore
8.40
自引率
2.20%
发文量
101
审稿时长
3-8 weeks
期刊介绍: Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice. The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.
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