Effect of training on motor abilities of heterozygous staggerer mutant (Rora +/Rora sg) mice during aging

Abstract

Heterozygous cerebellar mutant (Rora +/Rora sg) mice and control (Rora +/Rora +) mice of the same C57Bl6/J strain, 3–24 months old, were subjected to motor training on a rotorod for 10 days. Falling latency and percentage of time spent walking were measured. A good correlation was found between falling latency and walking time: the mice which maintained equilibrium for a long time were those which were walking, and the mice which fell early were those which were gripping suggesting that walking is obviously the most adapted strategy to keep balance on the rotorod. In Rora +/Rora + mice, scores before training were altered very precociously (from 6 months of age). Moreover, scores of Rora +/Rora sg mice were lower than those of Rora +/Rora + mice from the age of 3 months, while neuronal number in the cerebellar cortex of these mutants was quite normal and similar to that of Rora +/Rora + mice. This suggests that the motor skill disability would be due to fine structural and/or biochemical changes preceding neuronal death. Such subtle changes would begin several months earlier in Rora +/Rora sg than in Rora +/Rora + mice. Training on the rotorod resulted in increased scores in both genotypes at all ages. Motor learning abilities were therefore preserved in animals with a moderate neuronal loss in the cerebellum. It may be that motor learning is partly compensated by the striatum, which is known to play a major role in learning of motor skills.