Investigating the effects of prednisolone on behavior in mouse models of Duchenne muscular dystrophy

Abstract Background Next to progressive muscle loss, Duchenne muscular dystrophy patients suffer from behavioral and cognitive problems. This is due to mutations in the DMD gene, that result in the lack of dystrophin in both the muscles and brain. As part of the standards of care, patients receive corticosteroids (prednisolone or deflazacort) to slow down muscle degeneration. The precise consequences of chronic corticosteroid usage on the behavior of DMD patients remain unclear, mainly due to challenges of recruiting corticosteroid naïve patients into clinical studies. Objective This study used DMD mouse models, representing mutations resulting in lack of one or more dystrophin isoforms, to analyze the effects of corticosteroid treatment on different behavioral domains. Methods Prednisolone (PDN) or placebo was administered via a subcutaneous 60-day slow release pellet (66 µg/day) and mice were subjected to several behavioral tests. Results Unfortunately, the pellet only exposed mice to PDN for half of the intended duration. During the time of PDN exposure, we found a small amelioration in anxiety but were unable to find any differences in social interaction and spatial learning and memory. Conclusions Short term exposure to PDN via a slow release pellet does not seem to negatively affect anxiety, social interaction or spatial learning and memory. We cannot rule out that a longer treatment period than 4 weeks would affect behavior in DMD mice.