title: Dystonia and cerebellar degeneration in the leaner mouse mutant.
abstract: Cerebellar degeneration is traditionally associated with ataxia. Yet, there are examples of both ataxia and dystonia occurring in individuals with cerebellar degeneration. There is also substantial evidence suggesting that cerebellar dysfunction alone may cause dystonia. The types of cerebellar defects that may cause ataxia, dystonia, or both have not been delineated. In the current study, we explored the relationship between cerebellar degeneration and dystonia using the leaner mouse mutant. Leaner mice have severe dystonia that is associated with dysfunctional and degenerating cerebellar Purkinje cells. Whereas the density of Purkinje cells was not significantly reduced in 4 week-old leaner mice, approximately 50% of the neurons was lost by 34 weeks of age. On the other hand, the dystonia and associated functional disability became significantly less severe during this same interval. In other words, dystonia improved as Purkinje cells were lost, suggesting that dysfunctional Purkinje cells, rather than Purkinje cell loss, contribute to the dystonia. These results provide evidence that distorted cerebellar function may cause dystonia and support the concept that different types of cerebellar defects can have different functional consequences.
authors: Emory University School of Medicine, Department of Pharmacology, Woodruff Memorial Research Building, 101 Woodruff Circle, Atlanta, GA 30322, United States.
authors: Robert S
authors: RS
authors: Raike
authors: Emory University School of Medicine, Department of Pharmacology, Woodruff Memorial Research Building, 101 Woodruff Circle, Atlanta, GA 30322, United States; Emory University School of Medicine, Department of Neurology, Woodruff Memorial Research Building, 101 Woodruff Circle, Atlanta, GA 30322, United States. Electronic address: hjinnah@emory.edu.
authors: Ellen J
authors: EJ
authors: Hess
authors: Emory University School of Medicine, Department of Neurology, Woodruff Memorial Research Building, 101 Woodruff Circle, Atlanta, GA 30322, United States; Emory University School of Medicine, Department of Human Genetics, Woodruff Memorial Research Building, 101 Woodruff Circle, Atlanta, GA 30322, United States.
authors: H A
authors: HA
authors: Jinnah
mesh_terms: D000818:Animals; D002452:Cell Count; D002526:Cerebellar Diseases / Q000150:complications / Q000473:pathology*; D004421:Dystonia / Q000209:etiology / Q000473:pathology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D011689:Purkinje Cells / Q000473:pathology*
keywords: Cerebellum; Dystonia; Leaner; Purkinje cell