title: Subtle microstructural changes of the cerebellum in a knock-in mouse model of DYT1 dystonia.
abstract: The dystonias are a group of disorders characterized by involuntary twisting and repetitive movements. DYT1 dystonia is an inherited form of dystonia caused by a mutation in the TOR1A gene, which encodes torsinA. TorsinA is expressed in many regions of the nervous system, and the regions responsible for causing dystonic movements remain uncertain. Most prior studies have focused on the basal ganglia, although there is emerging evidence for abnormalities in the cerebellum too. In the current studies, we examined the cerebellum for structural abnormalities in a knock-in mouse model of DYT1 dystonia. The gross appearance of the cerebellum appeared normal in the mutant mice, but stereological measures revealed the cerebellum to be 5% larger in mutant compared to control mice. There were no changes in the numbers of Purkinje cells, granule cells, or neurons of the deep cerebellar nuclei. However, Golgi histochemical studies revealed Purkinje cells to have thinner dendrites, and fewer and less complex dendritic spines. There also was a higher frequency of heterotopic Purkinje cells displaced into the molecular layer. These results reveal subtle structural changes of the cerebellum that are similar to those reported for the basal ganglia in the DYT1 knock-in mouse model.
authors.affiliation: Department of Neurology, Emory University, Atlanta 30322, GA, USA.
authors.forename: Chang-Hyun
authors.initials: CH
authors.lastname: Song
authors.affiliation: Department of Neurology, Emory University, Atlanta 30322, GA, USA.
authors.forename: Doug
authors.initials: D
authors.lastname: Bernhard
authors.affiliation: Department of Neurology, Emory University, Atlanta 30322, GA, USA; Department of Pharmacology, Emory University, Atlanta 30322, GA, USA.
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Hess
authors.affiliation: Department of Neurology, Emory University, Atlanta 30322, GA, USA; Department of Human Genetics, Emory University, Atlanta 30322, GA, USA; Department of Pediatrics, Emory University, Atlanta 30322, GA, USA. Electronic address: hjinnah@emory.edu.
authors.forename: H A
authors.initials: HA
authors.lastname: Jinnah
mesh_terms: D000818:Animals; D002452:Cell Count; D002531:Cerebellum / Q000648:ultrastructure*; D049229:Dendritic Spines / Q000648:ultrastructure; D004195:Disease Models, Animal; D004421:Dystonia / Q000235:genetics / Q000473:pathology*; D005260:Female; D055879:Gene Knock-In Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones / Q000235:genetics*; D011689:Purkinje Cells / Q000648:ultrastructure
chemical_list: C491548:Dyt1 protein, mouse; D018832:Molecular Chaperones
keywords: AP; Anatomy; Cerebellum; DCN; Deep cerebellar neuron; GC; GCL; Golgi histochemistry; Heterotopic cells; MCL; Mouse mutant; PC; Purkinje cell; Purkinje cells; Stereology; WM; deep cerebellar nuclei; deletion of a single GAG codon in TOR1A gene; granule cell; granule cell layer; molecular cell layer; region from bregma in the anterior–posterior direction; white matter; ΔE