Increased Local Cerebral Glucose Utilization in the Basal Ganglia of the Rolling Mouse Nagoya

Abstract

Rolling mouse Nagoya (rolling), an experimental mutant mouse, is characterized by a marked incoordination of the hind limbs and disturbance of gait. These motor disturbances have been attributed to cerebellar dysfunction, and rolling, therefore, has been regarded as an animal model of hereditary cerebellar ataxia. However, definite evidence for this possibility has not yet been provided. In the present study, local cerebral glucose utilization (LCGU) was observed by means of the [14C]deoxyglucose method in rolling ( rol/rol), as well as in behaviorally normal heterozygotes (+/ rol) and normal controls (+/+), in order to study functional activity of the brain in these mice. A definite increase in LCGU was found in the globus pallidus, entopeduncular nucleus, subthalamic nucleus, and substantia nigra of rolling, bilaterally. A minimal decrease in LCGU was also found in the vermis of the cerebellum. These findings reflect the markedly hyperactive state of the basal ganglia and the minimally hypoactive state in the vermis of the cerebellum in rolling. It is concluded that the dysfunction in the basal ganglia is the major cause of the motor disturbances of rolling, and that rolling may be regarded as an animal model of extrapyramidal motor disturbance.