【Objective】NPSLE is an intractable autoimmune disease with neuropsychiatric symptoms, such as depression. Recent, studies reported that LPA reduces neuroinflammation. MRL/lpr mouse has been used as an animal model of NPSLE because of behavioral abnormalities. In this study, we examined the effects of LPA on NPSLE model mice.
【Methods】15-week-old MRL/lpr mice were treated with or without LPA for 2 weeks. In another study, the mice were pretreated with or without ki16425 (an antagonist of LPA receptors 1 and 3) and they were treated with LPA for 2 weeks. After treatment, the behavioral tests were performed as indices of depression. Histological examinations were performed in the harvested brain tissues.
【Conclusions】The treatment with LPA significantly reduced the depressive behaviors in MRL/lpr mice. Pretreatment with ki16425 negated the effects of LPA. The expressions of Iba1 and CD68 (microglial markers) were increased in the hippocampus and prefrontal cortex of MRL/lpr mice compared to controls and LPA treatment suppressed the increases of Iba1 and CD68. Pretreatment with ki16425 negated the inhibitory effects of LPA. These findings suggest that LPA receptor stimulation by LPA may suppress microglial activation and depressive behaviors in NPSLE model mice.