LAUSR

The pathogenesis of neuropsychiatric lupus (NPSLE) remains ill-defined due to limited access to tissue and the diversity and complexity of clinical manifestations with most evidence deriving from animal studies in MLR/lpr lupus-prone mouse.To phenotype and characterize the neuropsychiatric disease in New Zealand Black/White (NZΒ/W) F1 strain; a spontaneous lupus prone mouse which is characterized by systemic autoimmunity.Mice were tested in a comprehensive behavioral test battery to assess possible effects on general depressive-like disorders, anxiety, cognitive function and motor performance/coordination. The following tests were conducted in the same order for all subjects (All females, NZB/W strain n=13 and C57BL/6 n=14) at 3 and 6 months of age: Open field, Novel object recognition (NOR), Novel object location (NOL), Elevated plus maze (EPM), Rotarod, Tail suspension test (TST), Prepulse inhibition (PPI), and Sucrose preference test (SPT). For comparisons, statistical significance was indicated as a two-sided P<0.05.NZB/W mice at 3 months and 6 months of age exhibit depressive-like disorder as assessed by SPT and TST (P <0.05 and <0.0001, respectively). Anxiety-like phenotype was evident in lupus-prone mice at both time points based on EPM test (Graph 1). Open-field test revealed decreased locomotor activity and rotarod (Graph 2) showed impaired motor coordination in 3 month-old and 6 month-old NZB/W mice (P<0.001 and <0.01, respectively). NZB/W mice exhibit cognitive dysfunction at 3 and 6 months of age based on NOR test (P<0.05). No differences in cognitive function was observed between the two groups (P=0.11). Prepulse inhibition test revealed decreased sensorimotor gating in 3 month-old NZB/W mice, a difference not reaching statistical significance (P=.078). It was not possible to interpret correctly the PPI at second time point (6 months of age) due to age-related hearing loss in B6 at 6 month-old. NZB/W become more anxious over the course of the disease as assessed by EPM (3 mo. versus 6 mo. P<0.001, paired t-test, Graph 1).The NZB/W lupus-prone strain exhibit depressive-like behavior, anxiety, cognitive impairment and motor disturbances both at early and late stages of the disease. This polygenic murine model may be more suitable for investigating the autoimmunity-mediated neuroinflammation in human SLE.None declared