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, t he 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 neuron s 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 s how that there is no strict correlation between neuronal death in the cerebellar cortex and motor behavior on the rota rod. However, the dif ficulties 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 disor ders that probably precede neuronal death. Therefore, in the heterozyg ous staggerer, behavioral motor disturbance is a sign of cerebellar dy sfunction which appears earlier than alterations in neuronal number.