Rolling mouse Nagoya as a mutant animal model of basal ganglia dysfunction: determination of absolute rates of local cerebral glucose utilization.
In order to elucidate the neuronal mechanism of the motor disturbances of the Rolling mouse Nagoya (rolling), a neurological mutant mouse (genotype rol/rol) showing frequent lurching and falling over on walking, we determined absolute rates of local cerebral glucose utilization (LCGU) with the [14C]deoxyglucose method. The rates were compared with those of heterozygote (+/rol) with normal behavior, and of normal mice (+/+) of the same strain (C3Hf/Nga). Rolling showed marked and significant increases in LCGU in the structures of the basal ganglia such as the globus pallidus, entopeduncular nucleus, substantia nigra pars compacta and pars reticulata, and subthalamic nucleus, confirming our previous finding with semiquantitative LCGU determination. Additional significant but much less marked increases in LCGU of rolling were found in some structures of the brainstem and limbic system, such as the pedunculopontine nucleus, red nucleus, ventral tegmental area, lateral habenula, and CA1 and CA3 of the hippocampus. Although rolling has been regarded as an animal model of cerebellar ataxia, rolling showed no alterations of LCGU in the cerebellum. The heterozygote showed intermediate increases in LCGU between rolling and normal mice in the basal ganglia structures such as the globus pallidus, substantia nigra pars reticulata and subthalamic nucleus. Our findings indicate that rolling has a definite, genetically determined dysfunction of the basal ganglia. The primary site of the basal ganglia dysfunction might probably be in the striatum, involving both the neostriatum and limbic striatum, and resulting in secondary dysfunction in their target structures.
Yamaguchi
T
T
Department of Clinical Neurophysiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kato
M
M
Fukui
M
M
Akazawa
K
K
D000818:Animals; D001480:Basal Ganglia Diseases / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006579:Heterozygote; D008032:Limbic System / Q000378:metabolism*; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants
D005947:Glucose