Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Cleveland Clinic at Lerner College of Medicine at Case Western Reserve University, Cleveland, OH, USA.
Brain Behav Immun. 2021 May;94:175-184. doi: 10.1016/j.bbi.2021.02.010. Epub 2021 Feb 17.
Neuropsychiatric lupus (NPSLE), a manifestation of the autoimmune disease systemic lupus erythematosus (SLE), is characterized by psychiatric symptoms including anxiety and depression and upregulated autoantibodies. The B6.Nba2 spontaneous mouse model develops SLE, but has not previously been tested for NPSLE.
We investigated the NPSLE phenotype in male and female B6.Nba2 mice (n = 12 each) and age- and sex-matched B6 controls (n = 10 each) via behavioral assessments for anxiety, depression, and memory deficits. Serum anti-dsDNA, anti-nRNP, anti-DWEYS peptide reactive IgG autoantibody levels and soluble TWEAK levels were determined by ELISA. Hippocampal regions were stained for activated microglia and neurons.
Both male and female B6.Nba2 mice showed elevated anti-dsDNA IgG, anti-nRNP IgG and anti-DWEYS reactive antibodies, elevated serum soluble TWEAK levels, and a strong anxiety and depression phenotype (p < 0.05-0.0001). Male B6.Nba2 mice developed this phenotype at a slightly older age than females. Female B6.Nba2 mice displayed reduced numbers of neurons in the hippocampal region compared to female B6 controls (p < 0.05).
The B6.Nba2 mouse model recapitulates many known NPSLE phenotypes, making it a promising model to investigate the development of NPSLE in the context of SLE.
神经精神性狼疮（NPSLE）是系统性红斑狼疮（SLE）自身免疫性疾病的一种表现形式，其特征为包括焦虑和抑郁在内的精神症状，以及自身抗体的上调。B6.Nba2 自发性小鼠模型可发展为 SLE，但之前尚未对其进行 NPSLE 检测。
我们通过焦虑、抑郁和记忆缺陷的行为评估，对 B6.Nba2 雌雄小鼠（各 12 只）和年龄及性别匹配的 B6 对照（各 10 只）进行了 NPSLE 表型研究。通过 ELISA 测定血清抗 dsDNA、抗 nRNP、抗 DWEYS 肽反应性 IgG 自身抗体水平和可溶性 TWEAK 水平。对海马区进行激活小胶质细胞和神经元染色。
B6.Nba2 雌雄小鼠均表现出升高的抗 dsDNA IgG、抗 nRNP IgG 和抗 DWEYS 反应性抗体、升高的血清可溶性 TWEAK 水平以及强烈的焦虑和抑郁表型（p<0.05-0.0001）。雄性 B6.Nba2 小鼠比雌性 B6.Nba2 小鼠出现这种表型的年龄稍大。与雌性 B6 对照相比，雌性 B6.Nba2 小鼠的海马区神经元数量减少（p<0.05）。
B6.Nba2 小鼠模型再现了许多已知的 NPSLE 表型，使其成为 SLE 背景下研究 NPSLE 发展的有前途的模型。
