Features of Neuropsychiatric Lupus in Nba2 mouse model

Abstract

Abstract Background Neuropsychiatric lupus (NPSLE) is a poorly understood manifestation of the autoimmune disease systemic lupus erythematosus (SLE). NPSLE is characterized by symptoms including anxiety and depression, and recent data have suggested a pathogenic role for interferon-alpha (IFNα). Additionally, IFNα can diminish the production of the neurotransmitter serotonin, suggesting a causative link between IFNα and NPSLE. B6.Nba2 mice develop SLE in an IFNα-dependent manner making it a valuable model for the study of NPSLE. Methods Age-matched female B6.Nba2 and B6 mice were tested. Behavioral studies included open field testing (OFT), elevated plus maze (EPM), and fear conditioning (FC) tests for detection of anxiety-like behavior, and forced swim test (FST) for detection of depression-like behavior. Serum serotonin and dopamine levels were measured by ELISA and serotonin receptors were enumerated by IHC. Result Results from both OFT (p=0.001), EPM (p<0.05) and FC (p<0.05) tests supported a strong anxiety phenotype in B6.Nba2 female mice, while data from FST (p<0.05) suggested a depressive phenotype as well. B6.Nba2 females also showed significantly less serum serotonin (p<0.0001) and dopamine (p<0.05) levels than age-matched B6 females. Conclusion Our data suggests that the B6.Nba2 mouse model of SLE expresses an anxiety and depressive phenotype resembling NPSLE. Along with our previous data showing that IFNα levels are upregulated and required for disease development, our results suggest a positive correlation between IFNα, reduced serotonin, and an anxiety phenotype. Current studies are evaluating the effect of genetic IFNα-receptor manipulation in brain cells and the direct relationship between IFNα and NPSLE.