Treatment with FTY-720 reverses social recognition deficits without affecting clinical scores or impaired motor performance in EAE in SJL mice

Experimental autoimmune encephalomyelitis (EAE) serves as a disease model for aspects of human multiple sclerosis (MS). Our aim was to explore additional parameters that might be predictive for the study of disease progression, including score-free intervals. The effects of FTY-720 (0.5 mg/kg/day in drinking water) were investigated in rodent EAE models. Dark Agouti (DA) rats were immunized with rat spinal cord homogenate (rSCH), Lewis rats with guinea pig myelin basic protein (gpMBP)69–88 and C57Bl/6J mice with myelin oligodendrocyte glycoprotein (MOG)35–55. SJL/J mice were immunized with myelin proteolipid protein (PLP)139–151 peptide. Clinical scores were registered in all models. In SJL mice with relapsing-remitting EAE, we also performed behavioral tests: rotarod, gait analysis and grip strength. Between days 26–28, mice were examined, according to Crawley's sociability and preference for social novelty test, in a rectangular, three-chamber box. Prophylactic treatment (3 days post-immunization, p.i.) with FTY-720 prevented clinical scores in 3 of the EAE rodent models: DA and Lewis rats and C57Bl/6J mice. In contrast, neither prophylactic nor late therapeutic (18 days p.i.) treatment with FTY-720 reduced clinical scores nor reversed deficits in the rotarod test in SJL mice. However, FTY-720 had some subtle effects on motor functions and sociability in SJL mice. Prophylactic treatment with FTY-720 improved the gait, specifically it normalized the distance between the tip of the tail and floor. FTY-720 also improved manifestations of reduced social (re)cognition or preference for social novelty which were evident in vehicle treated EAE SJL mice. The data suggest that changes in behavioral parameters can be detected in absence of clinical scores, may be indicative of subtle drug effects and may have translational value for human MS.