Motor behavior of heterozygous staggerer mutant (+/sg) versus normal (+/+) mice during aging

Three- to 24-month-old heterozygous staggerer (+/sg) and control (+/+) C57B16 mice were subjected to a motor test on a rota rod rotating at 30 or 40 revolutions per minute. The scores were evaluated by the time during which they maintained their equilibrium without falling down. Although the scores of both +/sg and +/+ animals decreased with age, the scores of +/sg mice were constantly lower at 3, 6 and 12 months and this difference was already significant at 3 months, i.e., before the 30% loss of Purkinje cells, granule cells and inferior olivary neurons which occurs between 3 months and 1 year in the mutant. At 18 months and beyond, scores no longer differed in both groups. These results show that there is no strict correlation between neuronal death in the cerebellar cortex and motor behavior on the rota rod. However, the difficulties in maintaining their equilibrium on the rota rod observed in +/sg mice as young as 3 months, indicate a deficit in accurate motor control which could be due to subtle structural or neurochemical disorders that probably precede neuronal death. Therefore, in the heterozygous staggerer, behavioral motor disturbance is a sign of cerebellar dysfunction which appears earlier than alterations in neuronal number.