Karnopp Thaís Evelyn, Chapacais Gustavo Flores, Gasparini Maria Luísa, Dos Santos Natália Garcia, Freitas Vinicius da Silva, Piccoli Marina, Di Domenico Andressa Leite, Doria Lucas Denardi, de Souza Nikolas Mateus Pereira, Rieger Alexandre, Freitas Eduarda Correa, Visioli Fernanda, Monticielo Odirlei André
Laboratory of Autoimmune Diseases, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
Medical Sciences Postgraduate Program, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Clin Exp Immunol. 2025 Jan 21;219(1). doi: 10.1093/cei/uxae099.
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.
评估 pristane 诱导的狼疮(PIL)模型中的神经精神表现,以及评估维生素 D(vit-D)对 PIL 小鼠大脑的免疫调节作用。80 只雌性 BALB/c 小鼠被分为六组,进行为期 90 天(3 个月)和 180 天(6 个月)的实验:CO3、CO6(对照组),PIL3、PIL6(pristane 诱导的狼疮组),VD3 和 VD6(补充 1,25 - 二羟基维生素 D 的 PIL 组)。进行了强迫游泳、高架十字迷宫和巴恩斯迷宫等行为测试。通过免疫荧光评估 pVDR 的表达。通过双重染色荧光评估脑内 IgM 和 IgG 沉积。通过 ELISA 对血清 IL-6 和 IFN-α1 进行定量。还对免疫球蛋白进行了 AUC-ROC 曲线分析。PIL 组和 VD 组在强迫游泳测试中表现出抑郁样行为,在高架十字迷宫测试中表现出焦虑样行为。PIL 组在巴恩斯迷宫测试中还表现出认知和记忆障碍。此外,PIL 组和 VD 组血清 IFN-α1 水平较高,但 IL-6 水平未升高。补充 vit-D 的小鼠在 180 天后脑内 IgM 和 IgG 沉积减少,pVDR 表达增加。AUC-ROC 曲线显示脑内 IgM 和 IgG 具有高敏感性和特异性。我们在这个系统性红斑狼疮(SLE)模型中观察到了神经精神表现,有力地证实了 PIL 模型适合作为神经精神性狼疮(NPSLE)模型。Vit-D 能够减少脑内免疫球蛋白沉积,并影响所评估动物的血清 IL-6 水平。此外,它改善了记忆,但对抑郁样和焦虑样行为没有影响。