Background Neuropsychiatric lupus (NPSLE) is a common but poorly understood manifestation of systemic lupus erythematosus (SLE), affecting up to 80% of SLE patients. Current treatments include broad immunosuppression and symptomatic control rather than addressing pathogenesis. Current mouse models of NPSLE were developed by selective inbreeding until a complex genetic background resulted in spontaneous development of SLE. However, these models are not easily manipulated by genetic tools, which prevents elucidation of a more specific mechanism. We propose to establish the neurobehavioral phenotype of the B6.Nba2 spontaneous mouse model of SLE, known to depend on interferon (IFN)-. Interestingly, recent studies suggested that IFN- contributes to NPSLE by stimulating microglia, making it a promising potential drug target.
Methods Age- and sex-matched B6.Nba2 and B6 mice were tested (n=3–5). We used open field testing as a general measure of movement and anxiety-like behavior and elevated plus maze as a more specific measure of anxiety. A novel object placement test assessed spatial memory. Rotarod testing was used to characterize motor coordination, and the forced swim test assessed for depression-like behavior. Students t-test with Welchs correction was used for statistical analysis.
Results B6.Nba2 mice moved less distance and at a slower velocity and spent less time in the center of the open field than B6 mice (p=0.0005). To determine whether this was truly from anxiety or if it was a result of motor deficits, we ran elevated plus maze and rotarod tests. In the elevated plus maze, B6.Nba2 mice spent more time in the closed arms than B6 mice (<0.0001), reflecting increased anxiety. There were no differences motor coordination, supporting an anxiety phenotype leading to decreased movement in the open field. On novel object placement testing, there were no differences in time spent with the novel object. Lastly, the forced swim test revealed that B6.Nba2 mice spent more time immobile than B6 mice (p<0.02), suggesting a depressive-like behavior in B6.Nba2 mice.
Conclusions Our data suggest that the B6.Nba2 mouse model expresses a strong anxiety phenotype, a depressive phenotype, but no deficits in spatial memory. This observation warrants further exploration of the B6.Nba2 as a mouse model of NPSLE along with analyses of brain histology and morphology and future evaluations of the relationship between IFN-, autoantibody levels and neurological disease manifestations.
Funding Source(s): None
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